Insulin sensitivity and glucose effectiveness from three minimal models: effects of energy restriction and body fat in adult male rhesus monkeys

1 Wisconsin Primate Research Center, Madison 53715; and Departments of 3 Biostatistics and Medical Informatics, 6 Physiology, and 2 Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706; 4 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808; and 5 Department of Biostatistics, University of Alabama, Birmingham, Alabama 35294 Submitted 22 October 2002 ; accepted in final form 12 June 2003 The minimal model of glucose disappearance (MINMOD version 3; MM3) and both the one-compartment (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 = 12) on a semipurified diet to 70% of control (C) intake (ad libitum-fed monkeys; n = 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. biological models; body composition; dietary restriction Address for reprint requests and other correspondence: J. W. Kemnitz, Wisconsin Primate Research Center, 1220 Capitol Court, Madison, WI 53715.