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

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Abstract
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.