Effect of long-term caloric restriction on GLUT4,phosphatidylinositol- 3 kinase p85 subunit, and insulin receptorsubstrate-1 protein levels in rhesus monkey skeletal muscle

Abstract

Caloric restriction (CR), a reduction in calorie intake withoutmalnutrition, improves insulin sensitivity in various species, includingmice, rats, rhesus and cynomolgus monkeys, and humans. Skeletal muscle isquantitatively the most important tissue for blood glucose clearance.Therefore, we assessed the effect of 6 years of CR (30% reduction incalorie intake) in male rhesus monkeys (14-20 years old) on muscleexpression of several proteins involved in insulin action. Whole bodyinsulin sensitivity (assessed by Modified Minimal Model) was significantlyincreased in CR relative to Control monkeys. CR did not alter theexpression of GLUT4 glucose transporter or phosphatidylinositol-3 kinasep85 subunit (PI3K). Insulin receptor substrate-1(IRS-1) abundance tended tobe greater for CR compared to Control monkeys (p = .051), but correlationalanalysis revealed no association between IRS-1 and insulin sensitivity (r2= .075, p = .271). These findings indicate that the CR-induced increase ininsulin sensitivity in rhesus monkeys is unrelated to alterations in GLUT4,P13K, and IRS-1 abundance.