Abstract

Objective: To quantitate insulin sensitivity in lean and obese non-diabetic baboons and examine the underlying cellular/molecular mechanisms responsible for impaired insulin action in order to characterize a baboon model of insulin resistance.

Material/Methods: 20 baboons received a hyperinsulinemic euglycemic clamp, with skeletal muscle and visceral adipose tissue biopsies at baseline, 30 and 120 min after insulin. Genes and protein expression of key molecules involved in the insulin signaling cascade (insulin receptor, IRS-1, p85, PI3 kinase, Akt and AS160) were sequenced and insulin-mediated changes were analyzed.

Results: Overall, baboons show a wide range of insulin sensitivity (6.2 ± 4.8 mg/kg.min), and there is a strong inverse correlation between indices of adiposity and insulin sensitivity (r=−0.946 p<0.001 for % body fat; r=−0.72 p<0.001 for waist circumference). The genes and protein sequences analyzed were found to have ∼98% identity to those of man. Insulin-mediated changes in key signaling molecules were impaired both in muscle and adipose tissue in obese insulin-resistant compared to lean insulin-sensitive baboons.

Conclusion: The obese baboon is a pertinent non-human primate model to examine the underlying cellular/molecular mechanisms responsible for insulin resistance and eventual development of type 2 diabetes mellitus (T2DM).