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). We have used the β-adrenergic agent isoproterenol as a tool to assess the role of basal hyperglycemia in maintaining these islet responses of MOD. The acute insulin responses (AIR; mean Δ 2- to 4-min immunoreactive insulin) to 12 μg isoproterenol increased in eight MOD and eight controls when plasma glucose (PG) levels were increasedby glucose infusions. Although increases of PG were similar in the two groups, differences ofAIR of controls vs. those of MOD were magnified during glucose infusion: AIR, 40 ± 8vs. 20 ± 15 μU/ml,(mean ± SEM), 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 six controls (Δglucose, -11 ± 2 mg/dl; AAIR, -15 ± 3μU/ml, P < 0.01 vs. baseline AIR) and six MOD (Δglucose, -112 ± 21; ΔAIR, -11 ± 4, P < 0.05). For each subject, the potentiating effect of glucose on the AIR to isoproterenol was expressed as the slopeof the relationship between ΔPG from the fasting PG level and ΔAIR 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 subjectincreased (r = -0.87; P < 0.001). These findings indicate that the AIR to isoproterenol isregulated by the PG level, but that this potentiating effect of glucose isimpaired 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. We hypothesize that, in asimilar manner, basal hyperglycemia may compensate for abnormal glucose regulation of basal insulin secretion in these patients.