| We performed intravenous glucose tolerance tests (IVGTT) under ketamine anesthesia semi-annually or annually for 10 years during a multidimensional study of the effects of aging and adult-onset dietary restriction (DR) in male rhesus monkeys. DR was moderate at ∼30% less that of baseline intake of a semi-purified diet plus daily fruit. Diets of restricted (R) animals were supplemented with a micronutrient mix. Food was available to control (C) animals ad libitum for six to eight hours a day and all animals were individually housed to allow accurate food intake assessment. For the first nine years of the study, we employed Bergman's minimal model to analyze IVGTT data; we estimated indices of insulin sensitivity and glucose effectiveness, which reflect the abilities of insulin and glucose, respectively, to enhance glucose uptake into tissues and to inhibit glucose production. At the 10-year assessment, the animals were middle aged (∼19 yrs); we used glucose tracer data and the minimal models of Cobelli and colleagues to estimate insulin sensitivity and glucose effectiveness related only to glucose uptake. We simultaneously estimated prehepatic insulin secretory parameters. Over time, we found a consistent and profound reduction in fasting plasma insulin, insulin responses to glucose and an enhanced insulin sensitivity among R animals, while among C monkeys we observed low insulin sensitivity and elevated insulin levels. Lower fasting insulin levels were due to lower β-cell sensitivity to glucose among R monkeys and in the dynamic conditions of an IVGTT, the elevated insulin responses of certain obese, hypertriglyceridemic C animals were the result of greater sensitivity suggesting a profile reminiscent of syndrome X described in humans. We also found that body fat was an important mediator, as determined statistically, of the effect we have thus far attributed to DR, suggesting that the mechanism(s) by which DR alters variables of glucose regulation may be related to loss of fat mass. Regardless of its mechanism(s), the available evidence in several species such as rodents, monkeys and the limited studies with humans suggest that DR promotes a healthier physiological profile than does ad libitum caloric intake with increasing age. |
