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Insulin and Glucagon Secretion Are Suppressed Equally during Both Hyper- and Euglycemia by Moderate Hyperinsulinemia in Patients with Diabetes Mellitus^*

Division of Endocrinology and Metabolism, Institute of Clinical Medicine, University of Tsukuba Tsukuba, Ibaraki-ken 305, Japan

Address all correspondence and requests for reprints to: Yasuko Murayama, M.D., Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki-ken 305, Japan.

Hyper- and euglycemic clamp studies were performed in patients with noninsulin-dependent diabetes mellitus to examine the effects of exogenous insulin administration on insulin and glucagon secretion. Plasma glucose was kept at the fasting level [mean, 10.0 ± 0.2 (±SE) mmol/L; hyperglycemic clamp], and graded doses of insulin (1, 3, and 10 mU/kg·min, each for 50 min) were infused. The plasma C-peptide level gradually decreased from 523 ± 66 to 291 ± 43 pmol/L (n = 13; P < 0.005) by the end of the hyperglycemic clamp study. After 90 min of equilibration with euglycemia (5.4 ± 0.1 mmol/L; euglycemic clamp), the same insulin infusion protocol caused a similar decrease in the plasma C-peptide level. With the same glucose clamp protocol, physiological hyperinsulinemia for 150 min (676 ± 40 pmol/L), obtained by the infusion of 2 mU/kg·min insulin, caused suppression of the plasma C-peptide level from 536 ± 119 to 273 ± 65 pmol/L during hyperglycemia and from 268 ± 41 to 151 ± 23 pmol/L during euglycemia (n = 9; P < 0.005 in each clamp). Plasma glucagon was suppressed to a similar degree in both glycemic states.

These results demonstrate that 1) insulin secretion in noninsulin-dependent diabetes mellitus is suppressed by high physiological doses of exogenous insulin in both the hyper- and euglycemic states, the degree of inhibition being independent of the plasma glucose level; and 2) glucagon secretion is also inhibited by such doses of exogenous insulin.

^* This work was supported in part by a research grant from the University of Tsukuba Research Project and a grant-in-aid from the Ministry of Education in Japan (no. 63770843).

Received March 4, 1988.

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