Effect of exogenous insulin on glucose kinetics in rats with noninsulin-dependent diabetes

Noninsulin-dependent diabetes (NIDD) was induced in adult female rats by neonatal administration of streptozotocin. Despite elevated basal plasma glucose values in the postabsorptive state (196 +/- 16 mg/100 mL as compared to 118 +/- 7 in the controls), the glucose disappearance rate measured after the intravenous glucose load was not significantly lower in the diabetic than in control rats. In contrast, in vivo glucose-induced insulin release was drastically reduced, thus suggesting that endogenous insulin was more effective on the target tissues of the diabetic rats. Glucose kinetics (glucose production, utilization, and clearance) in response to intravenous insulin injection were studied in anesthetized postabsorptive diabetic and control female rats using [6-3H] glucose. With a maximal dose of insulin (0.5 U/kg body weight) no difference in blood glucose-lowering effect of insulin was found between the 2 groups. With 2 submaximal insulin doses (0.15 and 0.3 U/kg body weight), glucose production was inhibited more rapidly and more efficiently in diabetic rats than in control rats: 2 minutes after the 0.15 U/kg insulin injection, endogenous glucose production fell by 79 +/- 5% in the diabetics while being unchanged in the controls and the maximal decrease of glucose production after the same insulin injection was significantly greater in the diabetic rats (79 +/- 5% at 2 minutes) compared to the controls (33 +/- 4% at 6 min). The rise of glucose clearance in response to insulin was not significantly different in the 2 groups. These findings are discussed in view of the increased insulin clearance rate in these diabetic females.(ABSTRACT TRUNCATED AT 250 WORDS)