Physiological and molecular determinants of insulin action in the baboon

Alberto O. Chavez, Juan C. Lopez-Alvarenga, M. Elizabeth Tejero, Curtis Triplitt, Raul A. Bastarrachea, Apiradee Sriwijitkamol, Puntip Tantiwong, V. Saroja Voruganti, Nicolas Musi, Anthony G. Comuzzie, Ralph A. Defronzo, Franco Folli

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63 Scopus citations

Abstract

OBJECTIVE-To quantitate insulin sensitivity in lean and obese nondiabetic baboons and examine the underlying cellular/ molecular mechanisms responsible for impaired insulin action to characterize a baboon model of insulin resistance. RESEARCH DESIGN AND METHODS-Twenty baboons received a hyperinsulinemic-euglycemic clamp with skeletal muscle and visceral adipose tissue biopsies at baseline and at 30 and 120 min after insulin. Genes and protein expression of key molecules involved in the insulin signaling cascade (insulin receptor, insulin receptor substrate-1, p85, phosphatidylinositol 3-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 -1 · min -1), and there is a strong inverse correlation between indexes 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 with lean insulin-sensitive baboons. CONCLUSIONS-The obese baboon is a pertinent nonhuman primate model to examine the underlying cellular/molecular mechanisms responsible for insulin resistance and eventual development of type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)899-908
Number of pages10
JournalDiabetes
Volume57
Issue number4
DOIs
StatePublished - Apr 1 2008

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Chavez, A. O., Lopez-Alvarenga, J. C., Tejero, M. E., Triplitt, C., Bastarrachea, R. A., Sriwijitkamol, A., Tantiwong, P., Voruganti, V. S., Musi, N., Comuzzie, A. G., Defronzo, R. A., & Folli, F. (2008). Physiological and molecular determinants of insulin action in the baboon. Diabetes, 57(4), 899-908. https://doi.org/10.2337/db07-0790