A1 adenosine receptor partial agonist lowers plasma FFA and improves insulin resistance induced by high-fat diet in rodents.

Abstract

There is substantial evidence in the literature that elevated plasma free fatty acids (FFA) play a role in the pathogenesis of type 2 diabetes. CVT-3619 is a selective partial A(1) adenosine receptor agonist that inhibits lipolysis and lowers circulating FFA. The present study was undertaken to determine the effect of CVT-3619 on insulin resistance induced by high-fat (HF) diet in rodents. HF diet feeding to rats for 2 wk caused a significant increase in insulin, FFA, and triglyceride (TG) concentrations compared with rats fed chow. CVT-3619 (1 mg/kg) caused a time-dependent decrease in fasting insulin, FFA, and TG concentrations. Acute administration of CVT-3619 significantly lowered the insulin response, whereas glucose response was not different with an oral glucose tolerance test. Treatment with CVT-3619 for 2 wk resulted in significant lowering of FFA, TG, and insulin concentrations in rats on HF diet. To determine the effect of CVT-3619 on insulin sensitivity, hyperinsulinemic euglycemic clamp studies were performed in C57BL/J6 mice fed HF diet for 12 wk. Glucose infusion rate was decreased significantly in HF mice compared with chow-fed mice. CVT-3619 treatment 15 min prior to the clamp study significantly (P < 0.01) increased glucose infusion rate to values similar to that for chow-fed mice. In conclusion, CVT-3619 treatment lowers FFA and TG concentrations and improves insulin sensitivity in rodent models of insulin resistance.

• Authors: Arvinder K Dhalla, Mei Yee Wong, Peter J Voshol, Luiz Belardinelli, Gerald M Reaven
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 292 Issue 5 Pg. E1358-63 (May 2007) ISSN: 0193-1849 [Print] United States
• PMID: 17227958 (Publication Type: Journal Article)

Chemical References

• 2-(6-((2-hydroxycyclopentyl)amino)purin-9-yl)-5-((2-fluorophenylthio)methyl)oxolane-3,4-diol
• Adenosine A1 Receptor Antagonists
• Dietary Fats
• Fatty Acids, Nonesterified
• Insulin
• Triglycerides
• Glucose
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Adenosine A1 Receptor Antagonists
• Animals
• Dietary Fats (administration & dosage, metabolism)
• Fatty Acids, Nonesterified (blood)
• Glucose (metabolism)
• Glucose Tolerance Test
• Insulin (blood)
• Insulin Resistance (physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Rats
• Rats, Sprague-Dawley
• Triglycerides (blood)