Glucoreceptor mechanisms and the control of insulin release and biosynthesis.
The models proposed for the means whereby the B-cell recognises glucose and related compounds as signals for insulin release and biosynthesis are discussed. The observed correlations between rates of metabolism and insulin release and biosynthesis are consistent with the substrate-site hypothesis. For glucose itself, the enzymes catalysing the phosphorylation of the sugar provide an explanation for the major characteristics of the islet responses, but for N-acetylglucosamine evidence is presented that the sugar transport system fulfils this discriminatory role. Possible mechanisms whereby sugar metabolism may be linked to changes in Ca2+-handling are considered and evidence is given supporting a role for the cytosolic NADPH/NADP+ ratio and the islet content of phosphoenolpyruvate. The nature of the targets for cyclic AMP and Ca2+ is discussed and some properties of islet cAMP-dependent protein kinase are summarised. Evidence is presented for the presence of calmodulin in islets and the possible involvement of calmodulin in stimulus-secretion coupling. On the basis of these considerations a speculative hypothesis for the mechanisms involved in the B-cell responses to glucose is outlined.
D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011955:Receptors, Drug / Q000502:physiology*
D007328:Insulin; D011955:Receptors, Drug; D009243:NAD; D009249:NADP; D000242:Cyclic AMP; D011494:Protein Kinases; D005947:Glucose; D002118:Calcium; D000117:Acetylglucosamine