Regulation of biosynthesis, release and degradation of insulin in cultured rat islets

Abstract

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/dl 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 microU/islet; after culture at 50, 150 and 300 mg/dl glucose (in islets plus media): 253 +/- 25, 975 +/- 90 and 1030 +/- 96 microU/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.