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The regulation of glucose-induced insulin secretion by Pre-stimulus glucose level and tolbutamide in normal man

1981; Springer Science+Business Media; Volume: 21; Issue: 3 Linguagem: Inglês

10.1007/bf00252654

1432-0428

Roman Pfeifer, Ronald J. Graf, Jeffrey B. Halter, D. Porte,

Diabetes and associated disorders

The relationship between the pre-stimulus glucose level and immunoreactive insulin responses to a glucose challenge (20-g IV) was studied in normal subjects. When the steady-state pre-stimulus glucose concentration was lowered by a 0.33 mU· kg-1· min-1 insulin infusion or raised by a 900mg/ min glucose infusion, no effect on first phase insulin secretion (mean Δ 3–5 min insulin level) was observed. In contrast, the second phase response (10–60 min insulin area after glucose pulse) to intravenous glucose fell during insulin infusion and increased during the glucose infusion. Overall, a linear relationship was found between the change of pre-stimulus glucose level from the control to that during the insulin or glucose infusion and the change in second phase response (r=0.65, n = 14, p<0.02). The effect of tolbutamide infusion (7 mg·m-2· min-1) when compared with saline control was to increase both first phase (+54 ±13 mU/1, n=8, p <0.001, mean±SEM) and second phase (+972±256mU · mur-1 · 1-1, P<0.01) insulinsecretion. It is concluded that the first phase response to a glucose pulse is independent of the steady-state pre-stimulus glucose concentration and is directly enhanced by tolbutamide; in contrast, second phase is related to both the steady-state pre-stimulus glucose level and tolbutamide. These findings suggest that changes in basal or pre-stimulus plasma glucose during therapy with sulphonylurea drugs may be expected to influence the second phase insulin responses to glucose challenge.