Enhances insulin sensitivity -
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Comprehensive Physiology , 3 1 , 1— Haupt, D. Hyperglycemia and antipsychotic medications. The Journal of clinical psychiatry, 62 Suppl 27, 15— About the author Dr. View Author Bio. Glucose Latest articles. Insulin Resistance and Prediabetes: Symptoms, Risk Factors, and What You Can Do Leann Poston, MD, MBA, M.
Signos How to Improve Impaired Fasting Glucose Caitlin Beale, MS, RDN. Weight Loss. How Excess Insulin Is Associated with Excess Weight William Dixon, MD.
Can Seasonal Allergies Spike Blood Sugar? Danielle Kelvas, MD. 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.
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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.
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Conversely, both AMPK phosphorylation and protein content were unchanged in the skeletal muscle and epididymal adipose tissue of NCD-fed liraglutide-treated rats. However, no changes were observed in the epididymal adipose tissue Figure 3 C.
Conversely, AMPK phosphorylation and protein content were unchanged in the epididymal adipose tissue of HFD-fed liraglutide-treated rats Figure 3 D. Overall, these data are consistent with the results from the euglycemic-hyperinsulinemic clamp studies. Akt phosphorylation Ser A and C and AMPK phosphorylation Thr B and D in liver, skeletal muscle, and adipose tissue samples from NCD-fed A and B and HFD-fed C and D rats receiving a 7-day regimen of once-daily liraglutide injections.
The resulting homogenates were immunoblotted for phosphorylated Akt pAkt Ser , Akt, phosphorylated AMPK pAMPK Thr , and β-actin antibodies.
The bar graphs show data quantification by the ImageJ software for the results from liver, skeletal muscle, and adipose tissue. Data are expressed relative to control values. To investigate the molecular mechanisms underlying the liraglutide-induced increase in insulin sensitivity, we performed quantitative real-time PCR analysis on total RNA from liver tissue samples of NCD-fed and HFD-fed rats at the terminal stages of the euglycemic-hyperinsulinemic experiments.
We first measured the expression levels of glucosephophatase G6pase , which is a key enzyme in the gluconeogenic pathway.
These findings indicate that liraglutide suppresses gluconeogenesis in the liver under both normal glucose tolerance and insulin-resistant states.
Gluconeogenic G6pase [A] and lipogenic Fas [B], Acc [C], Acl [D], Scd-1 [E], Srebp-1c [F], and Glp-1r [G] expression during the euglycemic-hyperinsulinemic clamp studies in liver samples from NCD-fed and HFD-fed rats receiving a 7-day regimen of once-daily liraglutide injection.
Levels of Cyclophilin A Cph were used for the normalization of sample loading. Values are presented as mean ± SEM. Next, we measured the expression levels of fatty acid synthase Fas , acetyl-coenzyme A carboxylase Acc , ATP citrate lyase Acl , stearoyl-coenzyme A desaturase Scd -1, and sterol regulatory element-binding protein Srebp -1c in the livers of NCD-fed and HFD-fed rats at the terminal stage of the euglycemic-hyperinsulinemic experiments.
We confirmed that Glp-1 receptor was expressed in rat liver. However, liraglutide did not alter the expression levels of Glp-1 receptor in the livers of NCD-fed or HFD-fed rats Figure 4 G. These findings indicate that liraglutide suppresses lipogenesis in the liver during both normal glucose tolerance and insulin-resistant states.
Gross morphological differences in the livers were shown in Figure 5 A, lipid accumulation resulted in a pale discoloration of the liver. As shown in Figure 5 B, HFD consumption increased liver lipid content, which was significantly attenuated by liraglutide treatment.
This finding was further confirmed by the assessment of lipid accumulation using Oil red O staining Figure 5 B. These results indicated that liraglutide treatment reduced the development of hepatic steatosis. Lipid accumulation in liver samples from NCD-fed and HFD-fed rats receiving a 7-day regimen of once-daily liraglutide injections.
Basal liver tissue samples in the NCD-fed and HFD-fed rats receiving 0- and 0. A, Macroscopic images of the livers. C, Liver sections stained with Oil Red O. The liraglutide-treated rats exhibited significantly lower body weights than compared with the control rats.
To assess whether the effects of augmented insulin sensitivity by liraglutide treatment were dependent on the reduction in body weight, we examined the correlation between body weight and GIR.
Body weight was not correlated with GIR in both NCD-fed and HFD-fed rats injected with liraglutide Figure 6 , A and B.
Moreover, in HFD-fed rats, the regression line of the liraglutide group was located superior to the control group, suggesting that the augmented insulin sensitivity by liraglutide is independent of the reduction in body weight Figure 6 B. Relationship between body weight and GIR in NCD-fed A and HFD-fed B rats receiving a 7-day regimen of once-daily liraglutide injections.
Furthermore, we conducted a pair-feeding study to investigate whether the augmented insulin sensitivity by liraglutide treatment was depend on the reduction in body weight.
The amount of food intake decreased by The body weights of control rats pair-fed with the liraglutide-injected rats designated control rats on the NCD [ Figure 7 A] and HFD [ Figure 7 G] were similar to those of liraglutide-injected rats on NCD Figure 7 B and HFD Figure 7 H.
As shown in Figure 7 C, the GIR required to achieve euglycemia increased significantly by As shown in Figure 7 D, the IS-GDR was not significantly different among these groups. During the clamp studies, insulin inhibition of HGO was significantly enhanced by Under HFD conditions, the GIR required to achieve euglycemia increased significantly by As shown in Figure 7 J, the IS-GDR increased significantly by Basal HGO also decreased significantly by NCD- or HFD-pair-feeding studies.
GLP-1 receptor agonists like liraglutide are used for the treatment of diabetes and are thought to act primarily by regulating the secretion of islet hormones 3 , 4. On the other hand, a number of studies have suggested that GLP-1 may exert a glucoregulatory action on peripheral tissues independent of its pancreatic effect 25 — However, subsequent studies in humans have been conflicting with some confirming the extrapancreatic effects of GLP-1 signaling 28 , 29 and others negating it 30 , In this study, we studied the in vivo effect of the GLP-1 receptor agonist, liraglutide, on insulin sensitivity in lean and obese rats.
The rats were fed NCD or HFD for a total of 4 weeks and treated daily with liraglutide for 7 days before having their HGO and GIR measured using euglycemic-hyperinsulinemic clamps. NCD-fed rats that were administered liraglutide had increased GIR attributable almost entirely to a greater suppression of HGO.
HFD-fed rats that were administered liraglutide had increased GIR attributable to an increase in IS-GDR and a suppression of HGO. In addition, liraglutide treatment caused weight loss over 7 days. Larsen et al 32 have demonstrated that sc injections of liraglutide at 0.
Our results showed that liraglutide treatment significantly suppressed food intake and lowered body weight in NCD-fed Figure 7 , A and B and HFD-fed Figure 7 , G and I rats; body weights of liraglutide-treated and control rats were maintained at similarly levels by pair-feeding methods.
The anorectic effect of GLP-1 is mediated via a peripherally accessible site located either in the brainstem or on the vagal afferents. In rats, the inhibitory actions of GLP-1 on gastric motility is mediated via the vagus nerve However, direct inhibition of gastrin secretion as well as stimulation of somatostatin release may also affect gastric emptying To investigate whether the augmented insulin sensitivity by liraglutide treatment is dependent on body weight reduction, we examined the correlation between body weight and GIR.
According to our data Figure 6 , A and B , in which scatter plots are used to compare values of body weight and GIR, no correlation could be detected between body weight and GIR, suggesting that the effects on insulin sensitivity are independent of the reduction in body weight.
However, liraglutide treatment was found to decrease body weight in a dose-dependent manner. Therefore, it is possible that the modest reduction in body weight contributed in part to the improvement in insulin sensitivity. Therefore, we conducted a pair-feeding study under NCD and HFD conditions.
The pair-feeding study revealed that NCD-fed rats treated with liraglutide had increased GIR during the hyperinsulinemic clamp attributable to a greater suppression of HGO. HFD-fed rats treated with liraglutide had increased GIR attributable to a simultaneous increase in IS-GDR and suppression of HGO.
These results suggest that the effects of augmented insulin sensitivity by liraglutide treatment are independent of the reduction in body weight. Cellular measurements shed light on potential mechanisms of action of liraglutide treatment. AMPK is a heterotrimeric protein consisting of a catalytic subunit α and 2 noncatalytic subunits β and γ AMPK activation promotes translocation of glucose transporter type 4 to the plasma membrane, thus stimulating of glucose uptake In addition, AMPK can function upstream of Akt, at least in endothelial cells We found that liraglutide increased Akt and AMPK phosphorylation in the livers of NCD-fed rats and in the livers and muscles in HFD rats.
In addition, liraglutide suppressed genes associated with gluconeogenesis, such as G6pase, and lipogenesis, such as Fas, Acc, Acl, Scd-1, and Srebp-1c, in the livers of NCD-fed and HFD-fed rats.
Furthermore, we confirmed the expression of Glp-1 receptor mRNA in the liver by quantitative real-time PCR. These results suggest that liraglutide directly increases AMPK activity and inhibits gluconeogenesis and lipogenesis. Several studies have shown that the GLP-1 receptor is expressed in various cells and tissues, such as pancreatic islets, kidney, lung, heart, and multiple regions of the peripheral and central nervous system Furthermore, it has been reported that the receptor is present on human hepatocytes, where it has a direct role in improving hepatic steatosis 38 , In contrast, other investigators have failed to detect mRNA transcripts encoding a full-length Glp-1 receptor in human, rat, or mouse liver The expression of GLP-1 receptor in hepatocytes is controversial.
Alternatively, liraglutide may suppress hepatic HGO indirectly via changes in glucagon levels or via neuronal circuits; the potential contributions of these mechanisms to the GLP-1 receptor-dependent reduction of hepatic fat require further investigation. To summarize, we have shown that in normal glucose metabolism states, such as in NCD-fed rats, liraglutide enhances insulin sensitivity in the liver but not in the skeletal muscle.
We have also demonstrated that in diet-induced insulin-resistant states, such as those simulated in HFD-fed rats, liraglutide improves insulin resistance in both the liver and skeletal muscles. Furthermore, liraglutide also improves fatty liver in diet-induced insulin-resistant states.
We thank Atsuko Hashimoto and Hiroko Ohashi for their excellent technical assistance. This work was supported by a Grant-in-Aid for Challenging Exploratory Research H. and a Grant-in-Aid for Scientific Research H.
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Some dietary and Enhances insulin sensitivity habits senzitivity help prevent insulin resistance. Insulin resistance, a condition insjlin which antiviral herbs and spices cells stop sennsitivity properly to insulin, is incredibly common. In Sodium intake and hypertension, the prevalence of insulin resistance is However, certain dietary and lifestyle habits can dramatically improve or help prevent this condition. Insulin is a hormone that your pancreas secretes. It regulates the amounts of nutrients circulating in your bloodstream 2. Although insulin is mostly involved in blood sugar regulation, it also affects fat and protein metabolism 2.
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