Hyaluronidase-Induced Inhibition of the Insulinotropic Action of Sulfonylureas, Leucine, and Glucagon in Rodent Isolated Pancreatic Islets[*]

Abstract

Exposure of hamster pancreatic islets to hyaluronidase during isolation by means of collagenase inhibits the insulinotropic action of several chemically different sulfonylureas,leucine, and glucagon without affecting glucose-stimulated insulin secretion. This inhibition is reversible for tolbutamide and leucine but irreversible for glucagon. Hyaluronidase inhibits reversibly the insulinotropic action of tolbutamide without affecting that of glucose also in mouse and rat isolated pancreatic islets. These findings suggest the existence of functionally related pancreatic beta cell receptors for tolbutamide and leucine different from those for glucose and glucagon and illustrate the potential usefulness of hyaluronidase as an enzymatic probe applicable toward investigating the cellular mechanism of action of key insulinotropic agents.

Key words

Hyaluronidase - Insulinotropic Agents - Isolated Pancreatic Islets - Stimulated Insulin Secretion - Pancreatic Beta Cell Receptors

1 Supported in part by a research grant from The Upjohn Company, Kalamazoo, Michigan, U.S.A.

1 Supported in part by a research grant from The Upjohn Company, Kalamazoo, Michigan, U.S.A.