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A Difference in Mechanism by Which Leucine and Other Amino Acids Induce Insulin Release¹

Department of Internal Medicine (Division of Endocrinology and Metabolism and the Metabolic Research Unit), The University of Michigan Ann Arbor, Michigan 48104

Leucine, arginine, valine and a solution of 8 amino acids not containing leucine were administered intravenously to healthy subjects before and after administration of chlorpropamide. Leucine and arginine were administered to 9 patients with functioning pancreatic islet cell tumors. Infusions of arginine were given to healthy subjects before and after the intravenous administration of diazoxide. Leucine induced excessive release of insulin in all healthy subjects pretreated with chlorpropamide and in some of the patients with functioning islet cell tumors. On the other hand, insulin release was normal or reduced when these 2 groups of subjects received the other essential amino acids employed. Insulin release induced by the administration of arginine to healthy subjects was not suppressed by prior infusion of diazoxide. The results of these studies suggest that the mechanism by which leucine induces insulin release differs from the mechanism by which other essential amino acids induce release of insulin.

Supported in part by USPHS Grants AM 02244 and T-1 AM 5001, National Institute of Arthritis and Metabolic Diseases; 5 MO1-FR-42-05, Division of Research Facilities and Resources; and USPHS Career Research Award 5-K6-AM-14, 237.

¹ Presented in part before the 48th Annual Meeting of The Endocrine Society, Chicago, Ill., June 20–22, 1966 (1) and before the Laurentian Hormone Conference (2), Mont Tremblant, Quebec, August 28-September 2, 1966.

Received June 12, 1967.

Accepted July 28, 1967.

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