POTENTIATION OF INSULIN SECRETORY RESPONSES BY PLASMA-GLUCOSE LEVELS IN MAN - EVIDENCE THAT HYPERGLYCEMIA IN DIABETES COMPENSATES FOR IMPAIRED GLUCOSE POTENTIATION

Insulin secretory responses to nonglucose stimuli may be of normal magnitude in maturity-onset diabetics (MOD). The .beta.-adrenergic agent isoproterenol was used as a tool to assess the role of basal hyperglycemia in maintaining these islet responses of MOD. The acute insulin responses (AIR; mean .DELTA.2-4 min immunoreactive insulin) to 12 .mu.g isoproterenol increased in 8 MOD and 8 controls when plasma glucose (PG) levels were increased by glucose infusions. Although increases of PG were similar in the 2 groups, differences of AIR of controls vs. those of MOD were magnified during glucose infusion: AIR, 40 .+-. 8 vs. 20 .+-. 15 .mu.U[units]/ml, (mean .+-. SE), P < 0.05, baseline; and 263 .+-. 56 vs. 60 .+-. 20, P < 0.01, 900 mg/min glucose infusion. Conversely, infusion of insulin for 2 h lowered PG and inhibited the AIR to isoproterenol in 6 controls (.DELTA.glucose, -11 .+-. 2 mg/dl; .DELTA.AIR, -15 .+-. 3 .mu.U/ml, P < 0.01 vs. baseline AIR) and 6 MOD (.DELTA.glucose, -112 .+-. 21; .DELTA.AIR, -11 .+-. 4, P < 0.05). For each subject, the potentiating effect of glucose on the AIR to isoproterenol was expressed as the slope of the relationship between .DELTA.PG from the fasting PG level and .DELTA.AIR from the baseline AIR. These slopes of potentiation were lower in MOD than in controls (0.16 .+-. 0.06 vs. 1.58 .+-. 47; P < 0.01) and declined monoexponentially as the fasting PG level of each subject increased (correlation coefficient = -0.87; P < 0.001). The AIR to isoproterenol is regulated by the PG level, but this potentiating effect of glucose is impaired in MOD. The relationship between the degree of impairment (as assessed by the slope of potentiation) and the fasting PG level suggests that the presence of basal hyperglycemia in MOD tends to preserve islet responsiveness to nonglucose stimuli. In a similar manner, basal hyperglycemia may compensate for abnormal glucose regulation of basal insulin secretion in these patients.