Exenatide prevents fat‐induced insulin resistance and raises adiponectin expression and plasma levels
- 15 September 2008
- journal article
- research article
- Published by Wiley in Diabetes, Obesity and Metabolism
- Vol. 10 (10), 921-930
- https://doi.org/10.1111/j.1463-1326.2007.00832.x
Abstract
Exenatide (exendin-4) can reduce blood glucose levels, increase insulin secretion and improve insulin sensitivity through mechanisms that are not completely understood. In the present study, we examined the effects of exenatide treatment on glucose tolerance (intravenous glucose tolerance test), insulin sensitivity (euglycaemic-hyperinsulinaemic clamps), insulin signalling (insulin receptor substrate 1 tyrosine phosphorylation) and adipocytokine levels (visfatin and adiponectin) in high fat-fed rats. Administration of exenatide (0.5 or 2.0 mug/kg twice daily x 6 weeks) prevented high-fat diet (HFD)-induced increases in body weight, plasma free fatty acids, triglycerides and total cholesterol. Exenatide also prevented HFD-induced deterioration in peripheral and hepatic insulin sensitivity, insulin clearance, glucose tolerance and decreased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in fat and skeletal muscles. Interestingly, plasma visfatin levels decreased in exenatide-treated rats, whereas expression and plasma levels of adiponectin increased. These results indicate that chronic exenatide treatment enhances insulin sensitivity and protects against high fat-induced insulin resistance.This publication has 28 references indexed in Scilit:
- D-chiro-inositol and Insulin Resistance: An Allosteric Point of ViewPublished by Taylor & Francis Ltd ,2013
- Reduction of hepatic insulin clearance after oral glucose ingestion is not mediated by glucagon-like peptide 1 or gastric inhibitory polypeptide in humansAmerican Journal of Physiology-Endocrinology and Metabolism, 2007
- Obesity, Inflammation, and Insulin ResistanceGastroenterology, 2007
- Changes and Relations of Circulating Visfatin, Apelin, and Resistin Levels in Normal, Impaired Glucose Tolerance, and Type 2 Diabetic SubjectsExperimental and Clinical Endocrinology & Diabetes, 2006
- Short-term pioglitazone treatment prevents free fatty acid-induced hepatic insulin resistance in normal rats: Possible role of the resistin and adiponectinBiochemical and Biophysical Research Communications, 2006
- Effects of Rimonabant on Metabolic Risk Factors in Overweight Patients with DyslipidemiaThe New England Journal of Medicine, 2005
- Reduced insulin clearance contributes to the increased insulin levels after administration of glucagon-like peptide 1 in miceDiabetologia, 2005
- Effects of Exenatide (Exendin-4) on Glycemic Control Over 30 Weeks in Sulfonylurea-Treated Patients With Type 2 DiabetesDiabetes Care, 2004
- Milrinone, a selective phosphodiesterase 3 inhibitor, stimulatesl lipolysis, endogenous glucose production, and insulin secretionMetabolism, 2003
- Pharmacokinetic actions of exendin‐4 in the rat: Comparison with glucagon‐like peptide‐1Drug Development Research, 2001