Carbohydrate metabolism and the glucoreceptor mechanism.

Current views on the recognition of sugars as signals for insulin biosynthesis and release are discussed. Evidence is presented that the initial steps in the metabolism of N-acetyl-glucosamine differ from those in glucose metabolism in that for the former transport into the islet represents the rate-limiting step. Different enzymes phosphorylate these two sugar, but it is suggested that N-acetylglucosamine and glucose enter the beta-cell via the same carrier since 3-O-methylglucose is shown to be a competitive inhibitor of N-acetylglucosamine oxidation. Inhibitory effects on N-acetylglucosamine oxidation are also observed with caffeine, 3-isobutyl-methylxanthine and phloretin. Inhibition of N-acetylglucosamine metabolism is associated with inhibition of N-acetylglucosamine-stimulated insulin release and biosynthesis. Methylxanthines also inhibit uptake of 45Ca2+ by islet mitochondria. The possible physiological role of islet mitochondrial Ca2+ uptake in the regulation of beta-cell cytosolic Ca2+ concentration is discussed.