Insulin Secretion and Glucose Uptake by Isolated Islets of the Hamster Effect of Insulin, Proinsulin and C-Peptide[*]

Abstract

Isolated pancreatic islets of normal hamsters were perifused either in a closed or in a open system. When the buffer was recirculated and the endogenous insulin was allowed to accumulate, the islets secreted significantly less insulin than when the system was open and the endogenous insulin was washed away. The addition of monocomponent insulin or of proinsulin to the perfusion buffer significantly decreased insulin secretion. The inhibitory action of proinsulin was significantly greater than that of monocomponent insulin. C peptide had no effect. When pancreatic islets were incubated in a fixed volume of stationary buffer containing unlabeled glucose (1.0 mg or 3.0 mg/ml) and glucose-U-¹⁴C (1.0 μC/ml), the amount of insulin secreted and the ¹⁴ _C02 produced by each islet decreased progressively as the number of islets in the sample increased. Under these conditions, the concentration of insulin required to inhibit insulin secretion increased with the concentration of glucose in the medium. Proinsulin did not alter the incorporation of leucine-4.5-³ H into total extractable insulin (insulin + proinsulin). Thus, insulin and proinsulin appear to inhibit insulin release, but not insulin synthesis.

Key words

Insulin Secretion - Effect of Insulin - Effect of Proinsulin - Effect of C Peptide - Isolated Islets - Glucose Uptake - Insulin Synthesis - Insulin - Proinsulin - C Peptide

1 Aided by Grants No. AMO6034 and AM05474 from the National Institute of Arthritis, Metabolism and Digestive Diseases, National Institutes of Health, and by a grant from the Women's Guild of Sinai Hospital of Detroit. - Portions of this paper have been published in abstract form (Dunbar and Foa 1973).

1 Aided by Grants No. AMO6034 and AM05474 from the National Institute of Arthritis, Metabolism and Digestive Diseases, National Institutes of Health, and by a grant from the Women's Guild of Sinai Hospital of Detroit. - Portions of this paper have been published in abstract form (Dunbar and Foa 1973).

2 Some of the work described in this paper was done in partial fulfillment of the requirements for a M. S. degree in Physiology, Wayne State University.