The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. XIV. Glucose Regulation of Insular Biosynthetic Activity1

Abstract

The biosynthetic activity of the pancreatic β-cell was assessed by measuring the incorporation of labeled leucine in rat isolated islets, both immunological and chromatographic procedures being used to characterize the newly synthesized peptides. The conversion rate of proinsulin and the release of newly synthesized hormonal peptides were also evaluated. Glucose and rnannose, unlike galactose, fructose, ribose and xylitol stimulated (pro)insulin biosynthesis. A sigmoidal curve characterized the relationship between (pro)insulin synthesis and the glucose concentration of the incubation medium, the treshold value for the stimulant action of glucose being lower for insulin synthesis than for insulin release. Glucose preferentially stimulated the synthesis of hormonal peptides as distinct from that of other insular proteins. This preferential action was suppressed by mannoheptulose and 2-deoxyglucose, but unaffected by cycloheximide or dinitrophenol. Based on these observations, a model is proposed which could be used to identify specific alterations of the glucosensor mechanism in the β-cell. (Endocrinolog93: 1001, 1973)