Regulation of Biosynthesis, Release and Degradation of Insulin in Cultured Rat Islets¹)

Summary

In order to study the long-term influence of glucose on islet cell functions, biosynthesis of (pro)insulin (³H-leucine incorporation during 3h-incubation both at 50 and 300 mg/dl of glucose), release of insulin and somatostatin and degradation of intra-insular insulin were measured in isolated rat islets, cultured for 3 days at 50, 150 and 300 mg/dl glucose. After culture at 50 mg/di of glucose, (pro) insulin biosynthesis was very low during 3 h incubation in presence of either 50 or 300 mg/dl glucose; whereas, after culture at 300 mg/dl glucose, a sustained high rate of biosynthesis was observed.

This priming-effect concerning hormone release during incubation period, in relation to the previous glucose concentration of culture medium was better proportional for D-cells than for the B-cells. During the 3 days of culture, the percentual differences in hormone release at 50, 150 and 300 mg/dl of glucose were, altogether, also higher for somatostatin than for insulin. Insulin degradation was strongly enhanced during culture at 50 mg/dl glucose (total insulin before culture : 526 ± 57 μU/islet; after culture at 50,150 and 300 mg/dl glucose (in islets plus media): 253 ± 25, 975 ± 90 and 1030 ± 96 μU/islet, respectively). The glucose-priming of islet cells differed for the various cell functions. At low glucose concentration the pre-synthesized insulin (which was not needed then physiologically) was again degraded within the islet cells; at higher concentrations of glucose, increased stimulation of the B-cells seemed to be modified by the paracrine action of somatostatin.

Key words

Islet culture - Glucose-priming - Paracrine regulation - (Pro) Insulin biosynthesis - Insulin release - Insulin degradation - Somatostatin release