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Calories: What Is Insulin Resistance and Why Does it Matter? - Dr. Robert LustigSome dietary and lifestyle habits can help prevent insulin resistance. Insulin resistance, a condition in which ahd cells stop insulim properly to insulin, sensitivihy incredibly common.
In fact, the prevalence Metabolism and insulin sensitivity insulin resistance is However, abd dietary BMI for Men lifestyle habits can dramatically improve or help prevent sensitivitt condition.
Insulin is a hormone that your pancreas secretes. It regulates the amounts of jnsulin circulating in your bloodstream 2. Although insulin is mostly involved in blood sugar regulation, it also affects fat and Metabolism and insulin sensitivity metabolism 2.
When you eat a sensiticity that contains carbs Metaboliwm, the insulkn of insulij in your bloodstream increases. The cells in your pancreas B vitamins for skin health this increase and release insulin sfnsitivity your blood.
Insulin then travels around your bloodstream, Chamomile Tea for Mood Enhancement your cells to pick up sensitiviity from your blood. This Metabolosm helps regulate blood sugar levels amd prevent high blood sugar, insulih can have harmful effects Metabolism and insulin sensitivity left untreated 34.
However, cells sometimes stop responding to insulin correctly. This is sesnitivity insulin andd. When you have this sensitiviity, your pancreas produces even more Metabilism to lower your blood sugar levels. Metabolidm leads to high insulin levels in your blood, known Mstabolism hyperinsulinemia 5.
Over time, your cells may become increasingly resistant to insulin, resulting in a rise in both insulin and Metabolism and insulin sensitivity sugar levels. If your blood sugar levels exceed a certain threshold, you may receive a Metabolism and insulin sensitivity of type 2 diabetes.
If Metqbolism have insulin resistance, you insu,in low insulin sensitivity. Conversely, if you are sensitive to insulin, you have low insulin resistance inxulin. Insulin resistance occurs when your cells stop responding to the hormone insulin. This insuli higher insulin and Metabolidm sugar levels, potentially leading to type 2 diabetes.
One possible cause is increased levels of free fatty acids in your blood, which can cause Metabolism and insulin sensitivity to stop responding Metabolism and insulin sensitivity to insulin 8. Sensitivoty main causes of elevated free fatty acids are Strategies for maintaining glucose balance Metabolism and insulin sensitivity too many calories and the presence of Weight management diet body fat.
In fact, overeating, weight gain annd, and inzulin are all strongly associated with insulin resistance 910 an, Seensitivity fat, the harmful belly fat that can accumulate around your organs, may release many free fatty acids sesitivity your Mental agility boost, as well as inflammatory sensitiviy that drive sensitivit resistance 12 Sensitivihy insulin iinsulin is more common Metabolis people with overweight or obesity, anyone can develop it Black, Hispanic, Boost energy for better performance Asian individuals are at particularly high senwitivity The main causes of insulin resistance are overeating and increased body fat, especially in Metabloism Metabolism and insulin sensitivity area.
Other factors that can contribute include high sugar intake, inflammation, inactivity, and genetics. A healthcare wensitivity can use several methods to determine whether you have insulin resistance.
For example, high fasting insulin levels are a strong indicator of this condition A fairly accurate test called HOMA-IR can estimate insulin resistance based on your blood sugar and insulin levels There are also ways to measure blood sugar regulation more directly, such as an oral glucose tolerance test — but this takes several hours.
Your risk of insulin resistance increases greatly if you have overweight or obesity, especially if you have large amounts of belly fat 7. A skin condition called acanthosis nigricans, which causes dark spots on your skin, can also indicate insulin resistance Low HDL good cholesterol levels and high blood triglycerides are two other markers strongly associated with insulin resistance High insulin and blood sugar levels are key symptoms of insulin resistance.
Other symptoms include excess belly fat, high blood triglycerides, and low HDL good cholesterol levels. Insulin resistance is a hallmark of two very common conditions: metabolic syndrome and type 2 diabetes.
Metabolic syndrome is a group of risk factors associated with type 2 diabetes, heart disease, and other health conditions. Its symptoms include high blood triglycerides, high blood pressureexcess belly fat, high blood sugar, and low HDL good cholesterol levels You may be able to prevent metabolic syndrome and type 2 diabetes by stopping the development of insulin resistance.
Insulin resistance is linked to metabolic syndrome and type 2 diabetes, two common health conditions around the world. Insulin resistance is strongly associated with heart disease, which is the leading cause of death around the globe 28 Additionally, insulin resistance has been linked to an increased risk of developing major depressive disorder It is often possible to completely reverse insulin resistance by making the following lifestyle changes:.
Most of the habits on this list also happen to be associated with better overall health, a longer life, and protection against chronic disease.
Lifestyle strategies such as exercise, healthy eating, and stress management may help reduce or even reverse insulin resistance. Low carb diets may be beneficial for metabolic syndrome and type 2 diabetes — and this is partially mediated by reduced insulin resistance 4445 According to the American Diabetes Association, consumption of foods high in carbs and low in fat may actually worsen insulin resistance 7.
Additionally, low carb diets may support weight loss, which could help increase insulin sensitivity 7 Low carb diets involve limiting your intake of foods high in carbs or added sugar, including baked goods, grains, and sweets. Diets that are very low in carbohydrates, such as the ketogenic dietmay also improve blood sugar regulation and enhance insulin sensitivity 48 According to one review, following a ketogenic diet may help improve blood sugar regulation, decrease inflammation and fasting insulin level, and promote weight loss, all of which may be beneficial for people with insulin resistance Low carb and ketogenic diets may improve insulin resistance and support blood sugar regulation.
However, you should talk with a healthcare professional before making major changes to your diet. Insulin resistance may be one of the key drivers of many chronic conditions, including type 2 diabetes. You can improve this condition through lifestyle measures such as eating a balanced diet, staying active, and making an effort to maintain a moderate body weight.
Preventing insulin resistance may be among the most effective ways to live a longer, healthier life. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available.
VIEW ALL HISTORY. Find out the different types of basal insulin. Understand the benefits, how they're administered, and potential side effects. Read on to learn how your insulin needs may…. Insulin resistance doesn't have to turn into diabetes. Know about early signs and find out what you can do to identify the condition.
Some people claim that artificial sweeteners can raise blood sugar and insulin levels, and potentially even cause diabetes. If your doctor recommends you start taking insulin to manage type 2 diabetes, you may have some questions. Read on for guidance.
Diabetes hinders your ability to produce insulin. Without it, cells are starved for energy and must seek an alternate source, leading to serious…. Learn about the different types of medications that can increase the production of insulin in people with diabetes. A Quiz for Teens Are You a Workaholic?
How Well Do You Sleep? Health Conditions Discover Plan Connect. Skin Care. Nutrition Evidence Based Insulin and Insulin Resistance: The Ultimate Guide.
Medically reviewed by Kelly Wood, MD — By Kris Gunnars, BSc — Updated on December 7, Insulin basics. What causes insulin resistance? How to know if you have insulin resistance. Discover more about Type 2 Diabetes.
Related conditions. Relationship to heart health. Other ways to reduce insulin resistance. Low carb diets. The bottom line. How we reviewed this article: History. Dec 7, Written By Kris Gunnars. Nov 28, Medically Reviewed By Kelly Wood, MD.
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: Metabolism and insulin sensitivity| Understanding Insulin Resistance | To date, six mammalian CerS have been identified CerS that show different affinities for the fatty acid acyl-CoA chain length used for sphingomyelin N-acylation. Gastroenterol Res Pract Hypertension; diabetes; atherosclerosis and NASH: Cause or consequence? As a result of insulin resistance, the pancreas attempts to compensate by secreting increasing amounts of insulin, resulting in hyperinsulinemia [ 4 ]. CRP is another marker of inflammation associated with IR and metabolic diseases and is a widely used clinical biomarker. Nat Rev Mol Cell Biol 9 2 — |
| Do You Have Insulin Resistance? | Ceramide synthases as potential targets for therapeutic intervention in human diseases. Acta , — Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Peraldi, P. Tumor necrosis factor TNF -alpha inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase. A ceramide-centric view of insulin resistance. Ussher, J. Inhibition of de novo ceramide synthesis reverses diet-induced insulin resistance and enhances whole-body oxygen consumption. Diabetes 59 , — Deevska, G. Acid sphingomyelinase deficiency prevents diet-induced hepatic triacylglycerol accumulation and hyperglycemia in mice. Blouin, C. Plasma membrane subdomain compartmentalization contributes to distinct mechanisms of ceramide action on insulin signaling. Chalfant, C. Long chain ceramides activate protein phosphatase-1 and protein phosphatase-2A. Activation is stereospecific and regulated by phosphatidic acid. Bourbon, N. Ceramide-induced inhibition of Akt is mediated through protein kinase Czeta: implications for growth arrest. Hajduch, E. Targeting of PKCzeta and PKB to caveolin-enriched microdomains represents a crucial step underpinning the disruption in PKB-directed signalling by ceramide. Powell, D. Roles of diacylglycerols and ceramides in hepatic insulin resistance. Trends Pharmacol. Merrill, A. Jr Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics. Bergman, B. Muscle sphingolipids during rest and exercise: a C signature for insulin resistance in humans. Diabetologia 59 , — Chung, J. Intramyocellular ceramides: subcellular concentrations and fractional de novo synthesis in postabsorptive humans. Diabetes 66 , — Montgomery, M. Regulation of glucose homeostasis and insulin action by ceramide acyl-chain length: a beneficial role for very long-chain sphingolipid species. Raichur, S. CerS2 haploinsufficiency inhibits beta-oxidation and confers susceptibility to diet-induced steatohepatitis and insulin resistance. Obesity-induced CerS6-dependent C ceramide production promotes weight gain and glucose intolerance. Randle, P. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1 , — Goodpaster, B. Metabolic flexibility in health and disease. This comprehensive review discusses the mechanisms for insulin resistance induced by metabolic inflexibility in muscle and adipose tissue. Kelley, D. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes 49 , — References and show the evidence for and describe the concept of metabolic inflexibility in the development of insulin resistance. Guilherme, A. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Perry, R. Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes. This study shows that adipose inflammation-stimulated lipolysis increases the influx of acetyl-CoA into the liver, which activates pyruvate carboxylase and promotes hepatic gluconeogenesis, leading to hyperglycaemia. This occurs in insulin-resistant states such as obesity and T2DM. Zhang, H. Tumor necrosis factor-alpha stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. Diabetes 51 , — Grant, R. Fat in flames: influence of cytokines and pattern recognition receptors on adipocyte lipolysis. Adipocyte-specific overexpression of retinol-binding protein 4 causes hepatic steatosis in mice. Hepatology 64 , — Yang, Q. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Morigny, P. Adipocyte lipolysis and insulin resistance. Biochimie , — Aguer, C. Acylcarnitines: potential implications for skeletal muscle insulin resistance. Koves, T. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. This paper provides evidence of increased incomplete β-oxidation of lipids in states of insulin resistance and obesity, resulting in the accumulation of acylcarnitines. Muoio, D. Lipid-induced mitochondrial stress and insulin action in muscle. Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. Liepinsh, E. Decreased acylcarnitine content improves insulin sensitivity in experimental mice models of insulin resistance. Bene, J. Role of carnitine and its derivatives in the development and management of type 2 diabetes. Diabetes 8 , 8 Nurjhan, N. Increased lipolysis and its consequences on gluconeogenesis in non-insulin-dependent diabetes mellitus. Best, C. The effects of cholesterol and choline on liver fat. Li, Z. Phosphatidylcholine and choline homeostasis. Raubenheimer, P. A choline-deficient diet exacerbates fatty liver but attenuates insulin resistance and glucose intolerance in mice fed a high-fat diet. Diabetes 55 , — Meikle, P. Sphingolipids and phospholipids in insulin resistance and related metabolic disorders. van der Veen, J. The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease. Article CAS Google Scholar. A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects. Liu, S. A diurnal serum lipid integrates hepatic lipogenesis and peripheral fatty acid use. Rong, X. LXRs regulate ER stress and inflammation through dynamic modulation of membrane phospholipid composition. Singh, A. Identification of hepatic lysophosphatidylcholine acyltransferase 3 as a novel target gene regulated by peroxisome proliferator-activated receptor delta. Cash, J. Liver-specific overexpression of LPCAT3 reduces postprandial hyperglycemia and improves lipoprotein metabolic profile in mice. Diabetes 6 , e Drazic, A. The world of protein acetylation. Menzies, K. Protein acetylation in metabolism — metabolites and cofactors. Moussaieff, A. Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. Donohoe, D. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Cell 48 , — Cai, L. Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes. Cell 42 , — Wellen, K. ATP-citrate lyase links cellular metabolism to histone acetylation. Carrer, A. Impact of a high-fat diet on tissue acyl-coA and histone acetylation levels. Lerin, C. GCN5 acetyltransferase complex controls glucose metabolism through transcriptional repression of PGC-1alpha. Rodgers, J. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Sakai, M. The GCN5-CITED2-PKA signalling module controls hepatic glucose metabolism through a cAMP-induced substrate switch. Acetylation of glucokinase regulatory protein decreases glucose metabolism by suppressing glucokinase activity. Fang, S. The p acetylase is critical for ligand-activated farnesoid X receptor FXR induction of SHP. Kemper, J. FXR acetylation is normally dynamically regulated by p and SIRT1 but constitutively elevated in metabolic disease states. Ma, K. Farnesoid X receptor is essential for normal glucose homeostasis. Houtkooper, R. Sirtuins as regulators of metabolism and healthspan. Banks, A. SirT1 gain of function increases energy efficiency and prevents diabetes in mice. Pfluger, P. Sirt1 protects against high-fat diet-induced metabolic damage. Purushotham, A. Systemic SIRT1 insufficiency results in disruption of energy homeostasis and steroid hormone metabolism upon high-fat-diet feeding. Xu, F. Chalkiadaki, A. High-fat diet triggers inflammation-induced cleavage of SIRT1 in adipose tissue to promote metabolic dysfunction. Gillum, M. SirT1 regulates adipose tissue inflammation. White, A. Skeletal muscle-specific overexpression of SIRT1 does not enhance whole-body energy expenditure or insulin sensitivity in young mice. Diabetologia 56 , — High-fat diet-induced impairment of skeletal muscle insulin sensitivity is not prevented by SIRT1 overexpression. Qiang, L. Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Ppargamma. Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. Wang, R. Daitoku, H. Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity. Matsuzaki, H. Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation. Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1. Hirschey, M. SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Cell 44 , — Ahn, B. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Lombard, D. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Lantier, L. SIRT3 is crucial for maintaining skeletal muscle insulin action and protects against severe insulin resistance in high-fat-fed mice. Fernandez-Marcos, P. Muscle or liver-specific Sirt3 deficiency induces hyperacetylation of mitochondrial proteins without affecting global metabolic homeostasis. Hancock, C. High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Holloszy, J. References and provide evidence that impaired mitochondrial function may not be a causative factor for insulin resistance. Holloway, G. Regulation of skeletal muscle mitochondrial fatty acid metabolism in lean and obese individuals. Ryu, D. A SIRT7-dependent acetylation switch of GABPbeta1 controls mitochondrial function. Shin, J. SIRT7 represses Myc activity to suppress ER stress and prevent fatty liver disease. Yoshizawa, T. SIRT7 controls hepatic lipid metabolism by regulating the ubiquitin-proteasome pathway. Canto, C. Feng, D. A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism. Sun, Z. Hepatic Hdac3 promotes gluconeogenesis by repressing lipid synthesis and sequestration. Hong, S. Dissociation of muscle insulin sensitivity from exercise endurance in mice by HDAC3 depletion. Montgomery, R. Maintenance of cardiac energy metabolism by histone deacetylase 3 in mice. Diet-induced lethality due to deletion of the Hdac3 gene in heart and skeletal muscle. Wang, S. Insulin and mTOR pathway regulate HDAC3-mediated deacetylation and activation of PGK1. PLoS Biol. Yang, X. Protein O-GlcNAcylation: emerging mechanisms and functions. Metabolic regulation by lysine malonylation, succinylation, and glutarylation. Cell Proteomics 14 , — Choudhary, C. The growing landscape of lysine acetylation links metabolism and cell signalling. Resh, M. Fatty acylation of proteins: the long and the short of it. Guan, X. Understanding protein palmitoylation: biological significance and enzymology. China Chem. Yalovsky, S. Lipid modifications of proteins - slipping in and out of membranes. Trends Plant Sci. Ren, W. Proteomic analysis of protein palmitoylation in adipocytes. Adipocyte 2 , 17—28 Du, K. DHHC7 palmitoylates glucose transporter 4 Glut4 and regulates Glut4 membrane translocation. Glut4 palmitoylation at Cys plays a critical role in Glut4 membrane trafficking. Wei, X. De novo lipogenesis maintains vascular homeostasis through endothelial nitric-oxide synthase eNOS palmitoylation. Spinelli, M. Brain insulin resistance impairs hippocampal synaptic plasticity and memory by increasing GluA1 palmitoylation through FoxO3a. Turnbaugh, P. An obesity-associated gut microbiome with increased capacity for energy harvest. Schwiertz, A. Microbiota and SCFA in lean and overweight healthy subjects. Obesity Silver Spring 18 , — Article Google Scholar. Ridaura, V. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science , References and provide evidence of altered gut microbiota in obesity and insulin resistance and show that this increases the propensity to develop obesity and insulin resistance. Vrieze, A. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology , — e Todesco, T. Propionate lowers blood glucose and alters lipid metabolism in healthy subjects. Venter, C. Effects of dietary propionate on carbohydrate and lipid metabolism in healthy volunteers. Chambers, E. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut 64 , — De Vadder, F. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell , 84—96 den Besten, G. Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARgamma-dependent switch from lipogenesis to fat oxidation. Frost, G. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58 , — Acetate mediates a microbiome-brain-beta-cell axis to promote metabolic syndrome. Ang, Z. GPR41 and GPR43 in obesity and inflammation — protective or causative? Brown, A. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. Canfora, E. Short-chain fatty acids in control of body weight and insulin sensitivity. Karaki, S. Expression of the short-chain fatty acid receptor, GPR43, in the human colon. Thangaraju, M. GPRA is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. Jiang, L. Increased brain uptake and oxidation of acetate in heavy drinkers. Al-Lahham, S. Regulation of adipokine production in human adipose tissue by propionic acid. Xiong, Y. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR Freeland, K. Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-alpha. Psichas, A. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Tolhurst, G. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61 , — Aberdein, N. Sodium acetate decreases phosphorylation of hormone sensitive lipase in isoproterenol-stimulated 3T3-L1 mature adipocytes. Adipocyte 3 , — Ge, H. Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Arpaia, N. Metabolites produced by commensal bacteria promote peripheral regulatory T cell generation. Maslowski, K. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR Propionic acid affects immune status and metabolism in adipose tissue from overweight subjects. Liu, T. Short-chain fatty acids suppress lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines through inhibition of NF-kappaB pathway in RAW Inflammation 35 , — Cox, M. Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E 2 and cytokines. World J. Li, G. Short-chain fatty acids enhance adipocyte differentiation in the stromal vascular fraction of porcine adipose tissue. Dewulf, E. Evaluation of the relationship between GPR43 and adiposity in human. Hong, Y. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR Priyadarshini, M. An acetate-specific GPCR, FFAR2, regulates insulin secretion. Felig, P. Plasma amino acid levels and insulin secretion in obesity. Cheng, S. Adipose tissue dysfunction and altered systemic amino acid metabolism are associated with non-alcoholic fatty liver disease. Iwasa, M. Elevation of branched-chain amino acid levels in diabetes and NAFL and changes with antidiabetic drug treatment. Bhattacharya, S. Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization. Atherosclerosis , — Shah, S. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Newgard, C. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Wurtz, P. Branched-chain and aromatic amino acids are predictors of insulin resistance in young adults. Diabetes Care 36 , — Metabolomics and metabolic diseases: where do we stand? This comprehensive review discusses the emerging roles of metabolites, especially BCAAs, in insulin resistance. Integrated metabolomics and genomics: systems approaches to biomarkers and mechanisms of cardiovascular disease. Interplay between lipids and branched-chain amino acids in development of insulin resistance. She, P. Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism. Wang, T. Metabolite profiles and the risk of developing diabetes. Lackey, D. Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity. Herman, M. Adipose tissue branched chain amino acid BCAA metabolism modulates circulating BCAA levels. Burrill, J. Inflammation and ER stress regulate branched-chain amino acid uptake and metabolism in adipocytes. Zimmerman, H. Adipose transplant for inborn errors of branched chain amino acid metabolism in mice. Shin, A. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism. Lefort, N. Increased reactive oxygen species production and lower abundance of complex I subunits and carnitine palmitoyltransferase 1B protein despite normal mitochondrial respiration in insulin-resistant human skeletal muscle. White, P. Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export. Pedersen, H. Human gut microbes impact host serum metabolome and insulin sensitivity. Lotta, L. Genetic predisposition to an impaired metabolism of the branched-chain amino acids and risk of type 2 diabetes: a Mendelian randomisation analysis. Smith, G. Protein ingestion induces muscle insulin resistance independent of leucine-mediated mTOR activation. Macotela, Y. Dietary leucine — an environmental modifier of insulin resistance acting on multiple levels of metabolism. PLoS ONE 6 , e Zeanandin, G. Differential effect of long-term leucine supplementation on skeletal muscle and adipose tissue in old rats: an insulin signaling pathway approach. Age Dordr 34 , — Xiao, F. Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice. Metabolism 63 , — Jang, C. A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Roberts, L. beta-Aminoisobutyric acid induces browning of white fat and hepatic beta-oxidation and is inversely correlated with cardiometabolic risk factors. Sun, H. Catabolic defect of branched-chain amino acids promotes heart failure. Circulation , — Li, T. Defective branched-chain amino acid catabolism disrupts glucose metabolism and sensitizes the heart to ischemia-reperfusion injury. Green, C. Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis. Su, X. Adipose tissue monomethyl branched-chain fatty acids and insulin sensitivity: effects of obesity and weight loss. Obesity Silver Spring 23 , — Malloy, V. Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer rats independent of energy restriction. Aging Cell 5 , — Stone, K. Mechanisms of increased in vivo insulin sensitivity by dietary methionine restriction in mice. Diabetes 63 , — Wanders, D. UCP1 is an essential mediator of the effects of methionine restriction on energy balance but not insulin sensitivity. FGF21 mediates the thermogenic and insulin-sensitizing effects of dietary methionine restriction but not its effects on hepatic lipid metabolism. Epner, D. Nutrient intake and nutritional indexes in adults with metastatic cancer on a phase I clinical trial of dietary methionine restriction. Cancer 42 , — Mentch, S. Histone methylation dynamics and gene regulation occur through the sensing of one-carbon metabolism. Chen, T. Tryptophan predicts the risk for future type 2 diabetes. PLoS ONE 11 , e Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss. Laferrere, B. Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss. Transl Med. Cotter, D. Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia. Puchalska, P. Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics. Taggart, A. D -beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. Kimura, I. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 GPR Shimazu, T. Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Goldberg, E. beta-Hydroxybutyrate deactivates neutrophil NLRP3 inflammasome to relieve gout flares. Youm, Y. The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Rheinheimer, J. Current role of the NLRP3 inflammasome on obesity and insulin resistance: A systematic review. Metabolism 74 , 1—9 Houstis, N. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Fisher, F. Understanding the physiology of FGF Foster, G. A randomized trial of a low-carbohydrate diet for obesity. Chavez, A. Circulating fibroblast growth factor is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance. Diabetes Care 32 , — Fazeli, P. FGF21 and the late adaptive response to starvation in humans. Douris, N. Beta-adrenergic receptors are critical for weight loss but not for other metabolic adaptations to the consumption of a ketogenic diet in male mice. Chavez-Talavera, O. Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease. Gastroenterology , — Preidis, G. Nutrient-sensing nuclear receptors PPARalpha and FXR control liver energy balance. Kawamata, Y. A G protein-coupled receptor responsive to bile acids. Maruyama, T. Identification of membrane-type receptor for bile acids M-BAR. Broeders, E. The bile acid chenodeoxycholic acid increases human brown adipose tissue activity. Watanabe, M. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Somm, E. beta-Klotho deficiency protects against obesity through a crosstalk between liver, microbiota, and brown adipose tissue. JCI Insight 2 , Fujisaka, S. Antibiotic effects on gut microbiota and metabolism are host dependent. Kumar, D. Activation of transmembrane bile acid receptor TGR5 modulates pancreatic islet alpha cells to promote glucose homeostasis. Thomas, C. TGR5-mediated bile acid sensing controls glucose homeostasis. Ding, L. Weber, G. Regulation of purine and pyrimidine metabolism by insulin and by resistance to tiazofurin. Enzyme Regul. Pelley, J. Purine, Pyrimidine, and Single Carbon Metabolism , Elsevier, Deng, Y. An adipo-biliary-uridine axis that regulates energy homeostasis. Science , eaaf Yamamoto, T. Relationship between plasma uridine and insulin resistance in patients with non-insulin-dependent diabetes mellitus. Nucleosides Nucleotides Nucleic Acids 29 , — Hamada, T. Plasma levels of uridine correlate with blood pressure and indicators of myogenic purine degradation and insulin resistance in hypertensive patients. Urasaki, Y. Chronic uridine administration induces fatty liver and pre-diabetic conditions in mice. Krylova, I. Effect of uridine on energy metabolism, LPO, and antioxidant system in the myocardium under conditions of acute coronary insufficiency. Le, T. Disruption of uridine homeostasis links liver pyrimidine metabolism to lipid accumulation. Hall, A. Abrogating monoacylglycerol acyltransferase activity in liver improves glucose tolerance and hepatic insulin signaling in obese mice. Agarwal, A. Endoplasmic reticulum stress promotes LIPIN2-dependent hepatic insulin resistance. TORC2 regulates hepatic insulin signaling via a mammalian phosphatidic acid phosphatase, LIPIN1. Schweitzer, G. Liver-specific loss of lipinmediated phosphatidic acid phosphatase activity does not mitigate intrahepatic TG accumulation in mice. Chibalin, A. Downregulation of diacylglycerol kinase delta contributes to hyperglycemia-induced insulin resistance. Zhang, C. Inhibited insulin signaling in mouse hepatocytes is associated with increased phosphatidic acid but not diacylglycerol. Jornayvaz, F. Hepatic insulin resistance in mice with hepatic overexpression of diacylglycerol acyltransferase 2. Monetti, M. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Choi, C. Suppression of diacylglycerol acyltransferase-2 DGAT2 , but not DGAT1, with antisense oligonucleotides reverses diet-induced hepatic steatosis and insulin resistance. Aburasayn, H. Targeting ceramide metabolism in obesity. Fayyaz, S. Involvement of sphingosine 1-phosphate in palmitate-induced insulin resistance of hepatocytes via the S1P2 receptor subtype. Diabetologia 57 , — Hu, W. Palmitate increases sphingosinephosphate in C2C12 myotubes via upregulation of sphingosine kinase message and activity. Kaiser, C. Acetylation of insulin receptor substrate-1 is permissive for tyrosine phosphorylation. BMC Biol. Cao, J. Endotoxemia-mediated activation of acetyltransferase P impairs insulin signaling in obesity. LaBarge, S. Is acetylation a metabolic rheostat that regulates skeletal muscle insulin action? Cells 38 , — Zhao, S. Regulation of cellular metabolism by protein lysine acetylation. Sundaresan, N. The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy. Signal 4 , ra46 Glidden, E. Multiple site acetylation of Rictor stimulates mammalian target of rapamycin complex 2 mTORC2 -dependent phosphorylation of Akt protein. Yu, J. Boutant, M. SIRT1 metabolic actions: integrating recent advances from mouse models. Download references. Nevertheless, there is growing evidence linking ectopic lipid accumulation, ER stress, plasma concentration of inflammatory cytokines, oxidative stress, abnormalities in insulin signaling, and other factors to IR. In recent years, the exploration of the molecular mechanisms of IR has also led to the emergence of new therapeutic concepts beyond metformin and TZD. Regardless lifestyle modification remains the most basic and least costly intervention. Normative criteria need to be developed for different metabolic diseases considering IR as a focus. FL and HJ provided the idea of the manuscript. XZ, XA, and CY contributed equally to this manuscript. XZ, XA, WS, and CY drafted the manuscript and searched the relevant literature. XZ and XA drafted the figures, and all authors approved the final version of the manuscript. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy. All authors contributed to the article and approved the submitted version. This work was supported by Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine. No: ZYYCXTD-D The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology 42 5 — doi: PubMed Abstract CrossRef Full Text Google Scholar. Sharma VR, Matta ST, Haymond MW, Chung ST. Measuring insulin resistance in humans. Horm Res Paediatr 93 — Muniyappa R, Madan R, Varghese RT. Assessing insulin sensitivity and resistance in humans. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, editors. South Dartmouth MA: MDText. com; Inc. Copyright © ; MDText. Google Scholar. Gar C, Rottenkolber M, Prehn C, Adamski J, Seissler J, Lechner A. Serum and plasma amino acids as markers of prediabetes; insulin resistance; and incident diabetes. Crit Rev Clin Lab Sci 55 1 — Park SE, Park CY, Sweeney G. Biomarkers of insulin sensitivity and insulin resistance: Past; present and future. Crit Rev Clin Lab Sci 52 4 — Milburn MV, Lawton KA. Application of metabolomics to diagnosis of insulin resistance. Annu Rev Med — Yang R, Hu Y, Lee CH, Liu Y, Diaz-Canestro C, Fong CHY, et al. PM20D1 is a circulating biomarker closely associated with obesity; insulin resistance and metabolic syndrome. Eur J Endocrinol 2 — Saklayen MG. The global epidemic of the metabolic syndrome. Curr Hypertens Rep 20 2 Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism — Steenblock C, Schwarz PEH, Ludwig B, Linkermann A, Zimmet P, Kulebyakin K, et al. COVID and metabolic disease: mechanisms and clinical management. Lancet Diabetes Endocrinol 9 11 — Younossi ZM, Golabi P, de Avila L, Paik JM, Srishord M, Fukui N, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J Hepatol 71 4 — Lonardo A, Nascimbeni F, Mantovani A, Targher G. Hypertension; diabetes; atherosclerosis and NASH: Cause or consequence? Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF diabetes atlas: Global; regional and country-level diabetes prevalence estimates for and projections for Diabetes Res Clin Pract Kaul K, Apostolopoulou M, Roden M. Insulin resistance in type 1 diabetes mellitus. Metabolism 64 12 — Nadeau KJ, Regensteiner JG, Bauer TA, Brown MS, Dorosz JL, Hull A, et al. Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function. J Clin Endocrinol Metab 95 2 — Cree-Green M, Newcomer BR, Brown MS, Baumgartner AD, Bergman B, Drew B, et al. Delayed skeletal muscle mitochondrial ADP recovery in youth with type 1 diabetes relates to muscle insulin resistance. Diabetes 64 2 — Schauer IE, Snell-Bergeon JK, Bergman BC, Maahs DM, Kretowski A, Eckel RH, et al. Insulin resistance; defective insulin-mediated fatty acid suppression; and coronary artery calcification in subjects with and without type 1 diabetes: The CACTI study. Diabetes 60 1 — Donga E, Dekkers OM, Corssmit EP, Romijn JA. Insulin resistance in patients with type 1 diabetes assessed by glucose clamp studies: systematic review and meta-analysis. Eur J Endocrinol 1 —9. Liu HY, Cao SY, Hong T, Han J, Liu Z, Cao W. Insulin is a stronger inducer of insulin resistance than hyperglycemia in mice with type 1 diabetes mellitus T1DM. J Biol Chem 40 — Ling C, Rönn T. Epigenetics in human obesity and type 2 diabetes. Cell Metab 29 5 — Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 46 1 :3— Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature —6. Rattarasarn C. Dysregulated lipid storage and its relationship with insulin resistance and cardiovascular risk factors in non-obese asian patients with type 2 diabetes. Adipocyte 7 2 — Pop A, Clenciu D, Anghel M, Radu S, Socea B, Mota E, et al. Insulin resistance is associated with all chronic complications in type 1 diabetes. J Diabetes. Pan Y, Zhong S, Zhou K, Tian Z, Chen F, Liu Z, et al. Association between diabetes complications and the triglyceride-glucose index in hospitalized patients with type 2 diabetes. J Diabetes Res Wang S, Shi J, Peng Y, Fang Q, Mu Q, Gu W, et al. Stronger association of triglyceride glucose index than the HOMA-IR with arterial stiffness in patients with type 2 diabetes: a real-world single-centre study. Cardiovasc Diabetol 20 1 Jia G, Whaley-Connell A, Sowers JR. Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease. Diabetologia 61 1 —8. Jia G, DeMarco VG, Sowers JR. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nat Rev Endocrinol 12 3 — Svensson M, Eriksson JW. Insulin resistance in diabetic nephropathy—cause or consequence? Diabetes Metab Res Rev 22 5 — Godsland IF. Insulin resistance and hyperinsulinaemia in the development and progression of cancer. Clin Sci Lond. Hernandez AV, Pasupuleti V, Benites-Zapata VA, Thota P, Deshpande A, Perez-Lopez FR. Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis. Eur J Cancer. Yin DT, He H, Yu K, Xie J, Lei M, Ma R, et al. The association between thyroid cancer and insulin resistance; metabolic syndrome and its components: A systematic review and meta-analysis. Int J Surg , — CrossRef Full Text Google Scholar. Kim NH, Chang Y, Lee SR, Ryu S, Kim HJ. Glycemic status; insulin resistance; and risk of pancreatic cancer mortality in individuals with and without diabetes. Am J Gastroenterol 11 —8. Pan K, Chlebowski RT, Mortimer JE, Gunter MJ, Rohan T, Vitolins MZ, et al. Insulin resistance and breast cancer incidence and mortality in postmenopausal women in the women's health initiative. Cancer 16 — Chiefari E, Mirabelli M, La Vignera S, Tanyolaç S, Foti DP, Aversa A, et al. Insulin resistance and cancer: In search for a causal link. Int J Mol Sci 22 Barber TM, Kyrou I, Randeva HS, Weickert MO. Mechanisms of insulin resistance at the crossroad of obesity with associated metabolic abnormalities and cognitive dysfunction. Int J Mol Sci 22 2. Mu N, Zhu Y, Wang Y, Zhang H, Xue F. Insulin resistance: a significant risk factor of endometrial cancer. Gynecol Oncol 3 —7. Arcidiacono B, Iiritano S, Nocera A, Possidente K, Nevolo MT, Ventura V, et al. Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms. Exp Diabetes Res Inoue M, Tsugane S. Insulin resistance and cancer: epidemiological evidence. Endocr Relat Cancer 19 5 :F1—8. Kong Y, Hsieh CH, Alonso LC. Front Endocrinol Lausanne Ramos-Lopez O, Riezu-Boj JI, Milagro FI, Martinez JA. DNA methylation signatures at endoplasmic reticulum stress genes are associated with adiposity and insulin resistance. Mol Genet Metab 1 —8. Kwa M, Plottel CS, Blaser MJ, Adams S. The intestinal microbiome and estrogen receptor-positive female breast cancer. J Natl Cancer Inst 8. Adeva-Andany MM, Martínez-Rodríguez J, González-Lucán M, Fernández-Fernández C, Castro-Quintela E. Insulin resistance is a cardiovascular risk factor in humans. Diabetes Metab Syndr 13 2 — Adeva-Andany MM, Fernández-Fernández C, Carneiro-Freire N, Castro-Quintela E, Pedre-Piñeiro A, Seco-Filgueira M. Insulin resistance underlies the elevated cardiovascular risk associated with kidney disease and glomerular hyperfiltration. Rev Cardiovasc Med 21 1 — Saely CH, Aczel S, Marte T, Langer P, Hoefle G, Drexel H. The metabolic syndrome; insulin resistance; and cardiovascular risk in diabetic and nondiabetic patients. J Clin Endocrinol Metab 90 10 — Zhang X, Li J, Zheng S, Luo Q, Zhou C, Wang C. Fasting insulin; insulin resistance; and risk of cardiovascular or all-cause mortality in non-diabetic adults: a meta-analysis. Biosci Rep 37 5. Eddy D, Schlessinger L, Kahn R, Peskin B, Schiebinger R. Relationship of insulin resistance and related metabolic variables to coronary artery disease: a mathematical analysis. Diabetes Care 32 2 —6. Novo G, Manno G, Russo R, Buccheri D, Dell'Oglio S, Morreale P, et al. Impact of insulin resistance on cardiac and vascular function. Int J Cardiol —9. Wang M, Li Y, Li S, Lv J. Endothelial dysfunction and diabetic cardiomyopathy. Front Endocrinol Nakamura M, Sadoshima J. Cardiomyopathy in obesity, insulin resistance and diabetes. J Physiol 14 — Qi Y, Xu Z, Zhu Q, Thomas C, Kumar R, Feng H, et al. Myocardial loss of IRS1 and IRS2 causes heart failure and is controlled by p38α MAPK during insulin resistance. Diabetes 62 11 — Razani B, Chakravarthy MV, Semenkovich CF. Insulin resistance and atherosclerosis. Endocrinol Metab Clin North Am 37 3 — Fernández-Real JM, Ricart W. Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 24 3 — Kim SH, Reaven G. Sex differences in insulin resistance and cardiovascular disease risk. J Clin Endocrinol Metab 98 11 :E— Robins SJ, Rubins HB, Faas FH, Schaefer EJ, Elam MB, Anderson JW, et al. Insulin resistance and cardiovascular events with low HDL cholesterol: the veterans affairs HDL intervention trial VA-HIT. Diabetes Care 26 5 —7. Abdul-Ghani MA, Jayyousi A, DeFronzo RA, Asaad N, Al-Suwaidi J. Insulin resistance the link between T2DM and CVD: Basic mechanisms and clinical implications. Curr Vasc Pharmacol 17 2 — Muzurović E, Mikhailidis DP, Mantzoros C. Non-alcoholic fatty liver disease; insulin resistance; metabolic syndrome and their association with vascular risk. Metabolism Valenti L, Bugianesi E, Pajvani U, Targher G. Nonalcoholic fatty liver disease: cause or consequence of type 2 diabetes? Liver Int 36 11 — Dongiovanni P, Stender S, Pietrelli A, Mancina RM, Cespiati A, Petta S, et al. Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver. J Intern Med 4 — PubMed Abstract Google Scholar. Watt MJ, Miotto PM, De Nardo W, Montgomery MK. The Liver as an Endocrine Organ-Linking NAFLD and Insulin Resistance. Endocr Rev Oct 1;40 5 Titchenell PMLazar MABirnbaum MJ. Unraveling the Regulation of Hepatic Metabolism by Insulin. Trends Endocrinol Metab 28 7 — Huang JF, Tsai PC, Yeh ML, Huang CF, Huang CI, Hsieh MH, et al. Risk stratification of non-alcoholic fatty liver disease across body mass index in a community basis. J Formos Med Assoc 1 Pt 1 — Enooku K, Kondo M, Fujiwara N, Sasako T, Shibahara J, Kado A, et al. Hepatic IRS1 and ß-catenin expression is associated with histological progression and overt diabetes emergence in NAFLD patients. J Gastroenterol 53 12 — Bugianesi E, Gastaldelli A, Vanni E, Gambino R, Cassader M, Baldi S, et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia 48 4 — Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 5 — Mantovani A, Byrne CD, Bonora E, Targher G. Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: A meta-analysis. Diabetes Care 41 2 — Shipovskaya AA, Dudanova OP, Kurbatova IV. The clinical significance of insulin resistance in non-diabetic patients with early forms of non-alcoholic fatty liver disease. Ter Arkh. Alemzadeh R, Kichler J, Calhoun M. Spectrum of metabolic dysfunction in relationship with hyperandrogenemia in obese adolescent girls with polycystic ovary syndrome. Eur J Endocrinol 6 —9. Macut D, Bjekić-Macut J, Rahelić D, Doknić M. Insulin and the polycystic ovary syndrome. Diabetes Res Clin Pract — Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 33 6 — Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, et al. Diagnosis and treatment of polycystic ovary syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 98 12 — Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS, Legro RS. Scientific statement on the diagnostic criteria; epidemiology; pathophysiology; and molecular genetics of polycystic ovary syndrome. Endocr Rev 36 5 — He FF, Li YM. Role of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome: a review. J Ovarian Res 13 1 Falcone T, Finegood DT, Fantus IG, Morris D. Androgen response to endogenous insulin secretion during the frequently sampled intravenous glucose tolerance test in normal and hyperandrogenic women. J Clin Endocrinol Metab 71 6 —7. Vrbikova J, Hill M, Bendlova B, Grimmichova T, Dvorakova K, Vondra K, et al. Incretin levels in polycystic ovary syndrome. Eur J Endocrinol 2 —7. Stepto NK, Cassar S, Joham AE, Hutchison SK, Harrison CL, Goldstein RF, et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Hum Reprod 28 3 — Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome PCOS : The hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev 37 5 — Clarembeau F, Bale G, Lanthier N. Cirrhosis and insulin resistance: current knowledge; pathophysiological mechanisms; complications and potential treatments. Fu YH, Liu WJ, Lee CL, Wang JS. Associations of insulin resistance and insulin secretion with bone mineral density and osteoporosis in a general population. Kobayashi H, Tokudome G, Hara Y, Sugano N, Endo S, Suetsugu Y, et al. Insulin resistance is a risk factor for the progression of chronic kidney disease. Clin Nephrol. Cree MG, Wolfe RR. Postburn trauma insulin resistance and fat metabolism. Am J Physiol Endocrinol Metab 1 :E1—9. Nagpal M, De D, Handa S, Pal A, Sachdeva N. Insulin resistance and metabolic syndrome in young men with acne. JAMA Dermatol 4 — Hsu CS, Wang PC, Chen JH, Su WC, Tseng TC, Chen HD, et al. Increasing insulin resistance is associated with increased severity and prevalence of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 34 8 — Carmelli D, Cardon LR, Fabsitz R. Clustering of hypertension; diabetes; and obesity in adult male twins: same genes or same environments? Am J Hum Genet 55 3 — Lin HF, Boden-Albala B, Juo SH, Park N, Rundek T, Sacco RL. Heritabilities of the metabolic syndrome and its components in the northern manhattan family study. Diabetologia 48 10 — Wan ZL, Huang K, Xu B, Hu SQ, Wang S, Chu YC, et al. Diabetes-associated mutations in human insulin: crystal structure and photo-cross-linking studies of a-chain variant insulin wakayama. Biochemistry 44 13 — Tager H, Given B, Baldwin D, Mako M, Markese J, Rubenstein A, et al. A structurally abnormal insulin causing human diabetes. Nature —5. Taylor SI, Kadowaki T, Kadowaki H, Accili D, Cama A, McKeon C. Mutations in insulin-receptor gene in insulin-resistant patients. Diabetes Care 13 3 — Verdecchia F, Akcan N, Dastamani A, Morgan K, Semple RK, Shah P. Unusual glycemic presentations in a child with a novel heterozygous intragenic INSR deletion. Horm Res Paediatr 93 6 — Brown AE, Walker M. Genetics of insulin resistance and the metabolic syndrome. Curr Cardiol Rep 18 8 Mercado MM, McLenithan JC, Silver KD, Shuldiner AR. Genetics of insulin resistance. Curr Diabetes Rep 2 1 — Al-Beltagi M, Bediwy AS, Saeed NK. Insulin-resistance in paediatric age: Its magnitude and implications. World J Diabetes. Kuglin B, Kolb H, Greenbaum C, Maclaren NK, Lernmark A, Palmer JP. The fourth international workshop on the standardisation of insulin autoantibody workshop. Diabetologia 33 10 —9. Bowden DW. Association of the PTPN1 gene with type 2 diabetes and insulin resistance. Discovery Med 4 24 — Alibegovic AC, Sonne MP, Højbjerre L, Hansen T, Pedersen O, van Hall G, et al. The t-allele of TCF7L2 rs associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest. Diabetes 59 4 — Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature — Freidenberg GR, Reichart D, Olefsky JM, Henry RR. Reversibility of defective adipocyte insulin receptor kinase activity in non-insulin-dependent diabetes mellitus. Effect weight loss. J Clin Invest. Abd El-Kader SM, Al-Jiffri OH. Impact of weight reduction on insulin resistance; adhesive molecules and adipokines dysregulation among obese type 2 diabetic patients. Afr Health Sci 18 4 — Mechanisms of insulin resistance in obesity. Front Med 7 1 — Hirosumi J, Tuncman G, Chang L, Görgün CZ, Uysal KT, Maeda K, et al. A central role for JNK in obesity and insulin resistance. Petersen KF, Shulman GI. Etiology of insulin resistance. Am J Med 5 Suppl 1 :S10—6. Schenk S, Saberi M, Olefsky JM. Insulin sensitivity: modulation by nutrients and inflammation. Machado FVC, Pitta F, Hernandes NA, Bertolini GL. Physiopathological relationship between chronic obstructive pulmonary disease and insulin resistance. Endocrine 61 1 — Cosio FG, Kudva Y, van der Velde M, Larson TS, Textor SC, Griffin MD, et al. New onset hyperglycemia and diabetes are associated with increased cardiovascular risk after kidney transplantation. Kidney Int 67 6 — Porrini E, Delgado P, Bigo C, Alvarez A, Cobo M, Checa MD, et al. Impact of metabolic syndrome on graft function and survival after cadaveric renal transplantation. Am J Kidney Dis 48 1 — Rizza RA, Mandarino LJ, Gerich JE. Cortisol-induced insulin resistance in man: impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor detect of insulin action. J Clin Endocrinol Metab 54 1 —8. Lopes PC, Fuhrmann A, Carvalho F, Sereno J, Santos MR, Pereira MJ, et al. Cyclosporine a enhances gluconeogenesis while sirolimus impairs insulin signaling in peripheral tissues after 3 weeks of treatment. Biochem Pharmacol 91 1 — Schäcke H, Döcke WD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 96 1 — Rafacho A, Ortsäter H, Nadal A, Quesada I. Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis; insulin resistance and diabetes. J Endocrinol 3 :R49— Rafacho A, Quallio S, Ribeiro DL, Taboga SR, Paula FM, Boschero AC, et al. The adaptive compensations in endocrine pancreas from glucocorticoid-treated rats are reversible after the interruption of treatment. Acta Physiol Oxf. Galicia-Garcia U, Jebari S, Larrea-Sebal A, Uribe KB, Siddiqi H, Ostolaza H, et al. Statin treatment-induced development of type 2 diabetes: From clinical evidence to mechanistic insights. Int J Mol Sci 21 Chang AM, Halter JB. Aging and insulin secretion. Am J Physiol Endocrinol Metab 1 :E7— Krentz AJ, Viljoen A, Sinclair A. Insulin resistance: a risk marker for disease and disability in the older person. Diabetes Med 30 5 — Resnick HE, Harris MI, Brock DB, Harris TB. American diabetes association diabetes diagnostic criteria; advancing age; and cardiovascular disease risk profiles: results from the third national health and nutrition examination survey. Diabetes Care 23 2 — Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW, Berg AH, et al. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? Diabetes 51 10 —8. Reznick RM, Zong H, Li J, Morino K, Moore IK, Yu HJ, et al. Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis. Cell Metab 5 2 —6. Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science —7. Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science —2. Vieira-Lara MA, Dommerholt MB, Zhang W, Blankestijn M, Wolters JC, Abegaz F, et al. Age-related susceptibility to insulin resistance arises from a combination of CPT1B decline and lipid overload. BMC Biol 19 1 Minokoshi Y, Kahn CR, Kahn BB. Tissue-specific ablation of the GLUT4 glucose transporter or the insulin receptor challenges assumptions about insulin action and glucose homeostasis. J Biol Chem 36 — Gancheva S, Jelenik T, Álvarez-Hernández E, Roden M. Interorgan metabolic crosstalk in human insulin resistance. Physiol Rev 98 3 — Severinsen MCK, Pedersen BK. Muscle-organ crosstalk: The emerging roles of myokines. Endocr Rev 41 4 — Horita S, Nakamura M, Suzuki M, Satoh N, Suzuki A, Seki G. Selective insulin resistance in the kidney. BioMed Res Int Ashraf A, Palakkott A, Ayoub MA. Anti-insulin receptor antibodies in the pathology and therapy of diabetes mellitus. Curr Diabetes Rev 17 2 — Hall C, Yu H, Choi E. Insulin receptor endocytosis in the pathophysiology of insulin resistance. Exp Mol Med 52 6 — Rivers SL, Klip A, Giacca A. NOD1: An interface between innate immunity and insulin resistance. Endocrinology 5 — Copps KD, White MF. Diabetologia 55 10 — Carvalho-Filho MA, Carvalho BM, Oliveira AG, Guadagnini D, Ueno M, Dias MM, et al. Double-stranded RNA-activated protein kinase is a key modulator of insulin sensitivity in physiological conditions and in obesity in mice. Endocrinology 11 — Hage Hassan R, Pacheco de Sousa AC, Mahfouz R, Hainault I, Blachnio-Zabielska A, Bourron O, et al. J Biol Chem 6 — Cimmino I, Lorenzo V, Fiory F, Doti N, Ricci S, Cabaro S, et al. A peptide antagonist of Prep1-p interaction improves ceramide-induced insulin resistance in skeletal muscle cells. Oncotarget 8 42 — Abdelsalam SS, Korashy HM, Zeidan A, Agouni A. The role of protein tyrosine phosphatase PTP -1B in cardiovascular disease and its interplay with insulin resistance. Biomolecules 9 7. Sevillano J, Sánchez-Alonso MG, Pizarro-Delgado J, Ramos-Álvarez MDP. Role of receptor protein tyrosine phosphatases RPTPs in insulin signaling and secretion. Zhou R, Guo Q, Xiao Y, Guo Q, Huang Y, Li C, et al. Endocrine role of bone in the regulation of energy metabolism. Bone Res 9 1 Conte C, Epstein S, Napoli N. Insulin resistance and bone: a biological partnership. Acta Diabetol 55 4 — Hevener AL, Zhou Z, Drew BG, Ribas V. The role of skeletal muscle estrogen receptors in metabolic homeostasis and insulin sensitivity. Adv Exp Med Biol — Hong SH, Choi KM. Sarcopenic obesity; insulin resistance; and their implications in cardiovascular and metabolic consequences. Int J Mol Sci 21 2. Du P, Fan B, Han H, Zhen J, Shang J, Wang X, et al. NOD2 promotes renal injury by exacerbating inflammation and podocyte insulin resistance in diabetic nephropathy. Kidney Int 84 2 — Lopez-Pastor AR, Gomez-Hernandez A, Diaz-Castroverde S, Gonzalez-Aseguinolaza G, Gonzalez-Rodriguez A, Garcia G, et al. Liver-specific insulin receptor isoform a expression enhances hepatic glucose uptake and ameliorates liver steatosis in a mouse model of diet-induced obesity. Dis Model Mech 12 2. Diaz-Castroverde S, Baos S, Luque M, Di Scala M, González-Aseguinolaza G, Gómez-Hernández A, et al. Prevalent role of the insulin receptor isoform a in the regulation of hepatic glycogen metabolism in hepatocytes and in mice. Diabetologia 59 12 — Diaz-Castroverde S, Gómez-Hernández A, Fernández S, García-Gómez G, Di Scala M, González-Aseguinolaza G, et al. Insulin receptor isoform a ameliorates long-term glucose intolerance in diabetic mice. Dis Model Mech 9 11 — Taniguchi CM, Emanuelli B, Kahn CR. Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol 7 2 — James DE, Stöckli J, Birnbaum MJ. The aetiology and molecular landscape of insulin resistance. Nat Rev Mol Cell Biol 22 11 — Fazakerley DJ, Krycer JR, Kearney AL, Hocking SL, James DE. Muscle and adipose tissue insulin resistance: malady without mechanism? J Lipid Res 60 10 — McArdle MA, Finucane OM, Connaughton RM, McMorrow AM, Roche HM. Mechanisms of obesity-induced inflammation and insulin resistance: insights into the emerging role of nutritional strategies. Front Endocrinol Lausanne. Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 18 3 — Boucher J, Kleinridders A, Kahn CR. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol 6 1. Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM. IRSmediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science —8. Donath MY, Dalmas É, Sauter NS, Böni-Schnetzler M. Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity. Cell Metab 17 6 — Nieto-Vazquez I, Fernández-Veledo S, Krämer DK, Vila-Bedmar R, Garcia-Guerra L, Lorenzo M. Insulin resistance associated to obesity: the link TNF-alpha. Arch Physiol Biochem 3 — Samuel VT, Shulman GI. Mechanisms for insulin resistance: common threads and missing links. Cell 5 — Chen K, Li F, Li J, Cai H, Strom S, Bisello A, et al. Induction of leptin resistance through direct interaction of c-reactive protein with leptin. Nat Med 12 4 — Yang M, Qiu S, He Y, Li L, Wu T, Ding N, et al. Genetic ablation of c-reactive protein gene confers resistance to obesity and insulin resistance in rats. Diabetologia 64 5 — Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of ikkbeta. Yin J, Peng Y, Wu J, Wang Y, Yao L. J Leukoc Biol 95 1 — Jialal I, Kaur H, Devaraj S. Toll-like receptor status in obesity and metabolic syndrome: a translational perspective. J Clin Endocrinol Metab 99 1 — Kim JJ, Sears DD. TLR4 and insulin resistance. Gastroenterol Res Pract Saberi M, Woods NB, de Luca C, Schenk S, Lu JC, Bandyopadhyay G, et al. Hematopoietic cell-specific deletion of toll-like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high-fat-fed mice. Cell Metab 10 5 — Kiechl S, Wittmann J, Giaccari A, Knoflach M, Willeit P, Bozec A, et al. Blockade of receptor activator of nuclear factor-κB RANKL signaling improves hepatic insulin resistance and prevents development of diabetes mellitus. Nat Med 19 3 — Kaneto H, Matsuoka TA, Nakatani Y, Kawamori D, Miyatsuka T, Matsuhisa M, et al. Oxidative stress; ER stress; and the JNK pathway in type 2 diabetes. J Mol Med Berl. Han MS, Perry RJ, Camporez JP, Scherer PE, Shulman GI, Gao G, et al. A feed-forward regulatory loop in adipose tissue promotes signaling by the hepatokine FGF Genes Dev 35 — Apostolopoulos V, de Courten MP, Stojanovska L, Blatch GL, Tangalakis K, de Courten B. The complex immunological and inflammatory network of adipose tissue in obesity. Mol Nutr Food Res 60 1 — Orliaguet L, Dalmas E, Drareni K, Venteclef N, Alzaid F. Mechanisms of macrophage polarization in insulin signaling and sensitivity. McNelis JC, Olefsky JM. Macrophages; immunity; and metabolic disease. Immunity 41 1 — |
| Metabolic syndrome | Cardiovasc Diabetol 20 1 Total body fat mass and fat-free mass FFM were determined by using dual-energy X-ray absorptiometry. Over the past years, our knowledge of the pathogenesis of IR and T2DM has improved, the development of new treatments of IR and metabolic syndrome have gained certain success, while the complexity of IR and the presence of multiple feedback loops make a challenge to the specific intervention. Downregulation of diacylglycerol kinase delta contributes to hyperglycemia-induced insulin resistance. The hormone resistin links obesity to diabetes. Statin treatment-induced development of type 2 diabetes: From clinical evidence to mechanistic insights. |
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