Exenatide prevents fat-induced insulin resistance and raises adiponectin expression and plasma levels

Diabetes Obes Metab. 2008 Sep;10(10):921-30. doi: 10.1111/j.1463-1326.2007.00832.x. Epub 2007 Dec 17.


Background: Exenatide (exendin-4) can reduce blood glucose levels, increase insulin secretion and improve insulin sensitivity through mechanisms that are not completely understood.

Methods: 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.

Results: 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.

Conclusions: These results indicate that chronic exenatide treatment enhances insulin sensitivity and protects against high fat-induced insulin resistance.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood*
  • Adiponectin / genetics
  • Animals
  • Blood Glucose / metabolism
  • Dietary Fats / adverse effects
  • Exenatide
  • Fatty Acids, Nonesterified / blood
  • Gene Expression / drug effects
  • Glucose
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Resistance*
  • Lipid Metabolism / drug effects
  • Nicotinamide Phosphoribosyltransferase / blood
  • Nicotinamide Phosphoribosyltransferase / genetics
  • Peptides / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Signal Transduction / drug effects
  • Venoms / therapeutic use*
  • Weight Gain / drug effects


  • Adiponectin
  • Blood Glucose
  • Dietary Fats
  • Fatty Acids, Nonesterified
  • Hypoglycemic Agents
  • Insulin
  • Peptides
  • Venoms
  • Exenatide
  • Nicotinamide Phosphoribosyltransferase
  • Glucose