Insulin biosynthesis and secretion.
Studies are presented which support the concept that a cell membrane localized glucoreceptor system is involved in the insulin secretory response to glucose and that the specific stimulation of insulin synthesis by glucose reflects effects at both the transcriptional and posttranscriptional level. After 48 hours of fasting the insulin secretory response to glucose is markedly reduced. This reduction is overcome by 24 hours of refeeding carbohydrate, but notprotein or fat, and is blocked by refeeding in the presence of an inhibitor of RNA synthesis. Although these studies clearly demonstrate an inducible glucoreceptor system, they do not permit conclusions regarding either its composition or location in the beta-cell. Phloridzin, a glycoside with a high affinity for glucose-carrier systems in plama membranes, stimulated basal insulin secretion sixfold. A large number of plant lectins were tested for ability to stimulate insulin release from isolated islets, and only mushroom lectin did so. The lectin concentration producing half-maximal hormone releaseis 3 x 10-7, a value in good agreement with the dissociation constant forlectin binding. Glucose stimulated insulin sythesis in isolated rat islets was determined to be partially inhibited by actinomycin D. The posttranscriptional effect was determined to be increased initiation of total islet mRNAas well as proinsulin mRNA. To futher quantitate the effect of glucose on proinsulin mRNA, immunoprecipitation of proinsulin synthesizing polysomes was accomplished. It appeared that proinsulin is synthesized on a mRNA accommodating six to eight ribosomes, and the size of the proinsulin mRNA is 10-11 S on sucrose gradients. This unexpectedly large size of the proinsulin mRNA is discussed.
D000818:Animals; D003609:Dactinomycin / Q000494:pharmacology; D004040:Dietary Carbohydrates; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D005947:Glucose / Q000494:pharmacology*; D006020:Glycopeptides / Q000097:blood; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D037102:Lectins / Q000494:pharmacology; D011132:Polyribosomes / Q000276:immunology / Q000378:metabolism; D011233:Precipitin Tests; D011384:Proinsulin / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug; D014158:Transcription, Genetic / Q000187:drug effects
D004040:Dietary Carbohydrates; D006020:Glycopeptides; D007328:Insulin; D037102:Lectins; D011955:Receptors, Drug; D003609:Dactinomycin; D012313:RNA; D011384:Proinsulin; D005947:Glucose