Relationship between changes in body composition and insulin responsiveness in models of the aging rat.

Increased body weight (BW) is one of several confounding factors that may contribute to the development of insulin resistance in human aging. Therefore aging-associated increase in BW was determined by 3H2O in Sprague-Dawley (S-D, n = 40) rats and was highly correlated with increased lean body mass (LBM), fat mass (FM), and plasma insulin and free fatty acid (FFA) levels (r2 > 0.850, P < 0.01 for all). Insulin (18 mU.kg-1.min-1) responsiveness (Rd; 270 +/- 10 mumol.kg LBM-1.min-1, P < 0.01) decreased by 17% between 2 and 4 mo but did not decline further at 14 mo. This decrease was inversely correlated with the increase in FM between 2 and 4 mo (r2 = 0.522, P < 0.05). The decline in Rd was accompanied by an approximately 20% decrease in glycolytic rate by 4 mo (P < 0.01) and in glycogen synthesis rate at 14 mo (P < 0.01) compared with 2-mo rats. Thus early impairment in intracellular glucose metabolism occurred concomitantly with an initial, rapid, and disproportionate increase in FM compared with LBM. Further increases in FM after 4 mo of age were not associated with a further decrease in insulin responsiveness in either S-D or Fischer 344 aging rats.