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

Abstract

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.

• Authors: L Li, G Yang, Q Li, X Tan, H Liu, Y Tang, G Boden
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 10 Issue 10 Pg. 921-30 (Sep 2008) ISSN: 1463-1326 [Electronic] England
• PMID: 18093209 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adiponectin (blood, 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, metabolism)
• Insulin Resistance
• Lipid Metabolism (drug effects)
• Nicotinamide Phosphoribosyltransferase (blood, 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)