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In a longitudinal study of the effects of moderate (70%) dietary restriction (DR) on aging, plasma glucose and insulin concentrations were measured from semiannual, frequently sampled intravenous glucose tolerance tests (FSIGTT) in 30 adult male rhesus monkeys. FSIGTT data were analyzed with Bergman's minimal model, and analysis of covariance revealed that restricted (R) monkeys exhibited increased insulin sensitivity (S(I), P < 0.001) and plasma glucose disappearance rate (K(G), P = 0.015), and reduced fasting plasma insulin (I(b), P < 0.001) and insulin response to glucose (AIR(G), P = 0.023) compared with control (C; ad libitum-fed) monkeys. DR reduced the baseline fasting hyperinsulinemia of two R monkeys, whereas four C monkeys have maintained from baseline, or subsequently developed, fasting hyperinsulinemia; one has progressed to diabetes. Compared with only the normoinsulinemic C monkeys, R monkeys exhibited similarly improved FSIGTT and minimal-model parameters. Thus chronic DR not only has protected against the development of insulin resistance in aging rhesus monkeys, but has also improved glucoregulatory parameters compared with those of otherwise normoinsulinemic monkeys.

. Insulin sensitivity and glucose effectiveness from three minimal models: effects of energy restriction and body fat in adult male rhesus monkeys. Am J Physiol Regul Integr Comp Physiol 285: R1340-R1354, 2003. First published July 3, 2003 10.1152/ ajpregu.00651.2002The minimal model of glucose disappearance (MINMOD version 3; MM3) and both the onecompartment (1CMM) and the two-compartment (2CMM) minimal models were used to analyze stable isotope-labeled intravenous glucose tolerance test (IVGTT) data from year 10 of a study of the effect of dietary restriction (DR) in male rhesus monkeys. Adult monkeys were energy restricted (R; n ϭ 12) on a semipurified diet to ϳ70% of control (C) intake (ad libitum-fed monkeys; n ϭ 12). Under ketamine anesthesia, fasting insulin levels were greater among C monkeys. Insulin sensitivity estimates from all models were greater in R than C monkeys, whereas glucose effectiveness estimates were not consistently greater in R monkeys. Fasting plasma glucose as well as hepatic glucose production and clearance rates did not differ between groups. Body fat, in part, statistically mediated the effect of DR to enhance insulin sensitivity indexes. Precision of estimation and intermodel relationships among insulin sensitivity and glucose effectiveness estimates were in the ranges of those reported previously for humans and dogs, suggesting that the models may provide valid estimates for rhesus monkeys as well. The observed insulin sensitivity indexes from all models, elevated among R vs. C monkeys, may be explained, at least in part, by the difference in body fat content between these groups after chronic DR.

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We examined the effects of dietary restriction (DR) and age on ss-cell function and peripheral insulin sensitivity in rhesus monkeys. A semipurified diet was provided either ad libitum for approximately 8 hours/day to controls (C) or as approximately 70% of baseline intake to restricted (R) animals for 10 years. The minimal model of C-peptide secretion and kinetics and the labeled 2-compartment minimal model of glucose kinetics were identified using plasma glucose, C-peptide, and insulin concentrations during an intravenous glucose tolerance test. R monkeys had less body fat, lower basal ss-cell sensitivity to glucose (Ø(b)), greater insulin sensitivity, and lower first-phase plasma insulin response. DR did not significantly affect first-phase and second-phase ss-cell sensitivity to glucose. Indices of body fatness were highly predictive of the effect of DR on Ø(b), fasting insulin concentration and insulin responses to glucose. Enhanced peripheral insulin sensitivity among R monkeys was strongly correlated with lower Ø(b).