Summary
The dose as well as the time kinetics of insulin and adenosine-3′,5′-monophosphate (cyclic AMP) responses to glucose were compared in pancreatic islets isolated from normal and diabetic Chinese hamsters. The insulin content in diabetic islets was about one-half that in normal islets. Insulin release in diabetic islets incubated for 10 min with glucose 60–1000 mg/l00 ml was from one-third to one-half that in normal islets. Glucose 1000 mg/l00 ml stimulated three-fold increases in insulin release without increasing the accumulation of [3H] cyclic AMP in either normal or diabetic islets prelabelled with [3H] adenine. However, in the presence of 1.0 mM of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), glucose 150 mg/l00 ml elicited significant increases of insulin release (+ 134%) and [3H] cyclic AMP accumulation in islets (+ 44%) and incubation medium (+ 48%) of islets of normal but not diabetic hamsters. Also, in perifusion experiments with 0.1 mM IBMX, glucose 500 mg/l00 ml produced threefold greater increases in insulin release and two-fold greater increases in efflux of cyclic AMP in normal than diabetic islets. By contrast with the lesser effects of glucose in diabetic islets, 1.0 mM IBMX increased islet and medium cyclic AMP, as well as insulin release, similarly in normal and diabetic islets. It is suggested that the impairment of glucose induced insulin release in islets of the diabetic Chinese hamster may be due to a defective interaction of glucose with the adenylate cyclase-cyclic AMP system in the pancreatic B cell.
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Yerganian, G., Meier, H.: Spontaneous hereditary diabetes mellitus in the Chinese hamster (Cricetulus griseus). Fed. Proc.18, 514–518 (1959)
Renold, A.E., Burr, I.: The pathogenesis of diabetes mellitus. Possible usefulness of spontaneous hyperglycemic syndromes in animals. Calif. Med.112, 23–24 (1970)
Dulin, W.E., Lund, G.H., Gerritsen, G.C.: Studies on diabetes in the Chinese hamster: [1] pancreatic and plasma insulin, [2] glucose metabolism by diaphragm and fat. Diabetes15, 523–524 (1966)
Sims, E. A. H., Landau, B. R.: Diabetes mellitus in the Chinese hamster. I. Metabolic and morphologic studies. Diabetologia3, 115–123 (1967)
Gerritsen, G.C., Dulin, W.E.: Characterization of diabetes in the Chinese hamster. Diabetologia3, 74–84 (1967)
Malaisse, W., Malaisse-Lagae, F., Gerritsen, G.C., Dulin, W.E., Wright, P.H.: Insulin secretion in vitro by the pancreas of the Chinese hamster. Diabetologia3, 109–114 (1967)
Chang, A.Y., Schneider, D.I.: Metabolic abnormalities in the pancreatic islets and livers of the diabetic Chinese hamster. Diabetologia6, 180–185 (1970)
Frankel, B.J., Gerich, J.E., Hagura, R., Fanska, R.E., Gerritsen, G.C., Grodsky, G.M.: Abnormal secretion of insulin and glucagon by the in vitro perfused pancreas of the genetically diabetic Chinese hamster. J. clin. Invest.53, 1637–1646 (1974)
Cerasi, E., Luft, R.: The effect of an adenosine-3′,5′- monophosphate diesterase inhibitor (Aminophylline) on the insulin response to glucose infusion in prediabetic and diabetic subjects. Horm. Metab. Res.1, 162–168 (1969)
Cerasi, E., Luft, R.: Diabetes mellitus — a disorder of cellular information transmission? Horm. Metab. Res.2, 246–249 (1970)
Charles, M.A., Fanska, R., Schmid, F.G., Forsham, P.A., Grodsky, G.M.: Adenosine-3′,5′-monophosphate in pancreatic islets: Glucose-induced insulin release. Science179, 569–571 (1973)
Grill, V., Cerasi, E.: Stimulation by D-glucose of cyclic adenosine-3′,5′-monophosphate accumulation and insulin release in isolated pancreatic islets of the rat. J. biol. Chem.249, 4196–4201 (1974)
Zawalich, W.S., Karl, R.C., Ferrendelli, J.A., Matschinsky, F.M.: Factors governing glucose-induced elevation of cyclic 3′: 5′ AMP levels in pancreatic islets. Diabetologia11, 231–235 (1975)
Capita, K., Hedeskov, C.J.: The effect of starvation on phosphodiesterase activity and the content of adenosine 3′: 5′-cyclic monophosphate in isolated mouse pancreatic islets. Biochem. J.142, 653–658 (1974)
Hellman, B., Wahl, L.-A., Lernmark, Å., Taljedal, I.-B.: The pancreatic beta cell recognition of insulin secretagogues: Does cyclic AMP mediate the effect of glucose? Proc. nat. Acad. Sci. (Wash.)71, 3405–3409 (1974)
Moskalewski, S.: Isolation and culture of the islets of Langerhans of the guinea pig. Gen. comp. Endocr.5, 342–353 (1965)
Kikuchi, M., Rabinovitch, A., Blackard, W.G., Renold, A.E.: Perifusion of pancreas fragments: A system for the study of dynamic aspects of insulin secretion. Diabetes23, 550–559 (1974)
Krishna, G., Weiss, B., Brodie, B.B.: A simple sensitive method for the assay of adenyl cyclase. J. Pharmacol. exp. Ther.163, 379–385 (1968)
Grill, V.: Glucose-induced cyclic AMP accumulation in islets of Langerhans: Its relation to insulin release. Thesis, Stockholm: Karolinska Institute 1975
Herbert, V., Lau, K.-S., Gottlieb, C.W., Bleicher, S.J.: Coated-charcoal immunoassay of insulin. J. clin. Endocr.25, 1375–1384 (1965)
Hunter, W.M., Greenwood, F.C.: Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature (Lond.)194, 495–496 (1962)
Scott, D.A., Fisher, A.M.: The insulin and zinc content of normal and diabetic pancreas. J. clin. Invest.17, 725–728 (1938)
Bergmeyer, H.U., Bernt, E.: D-glucose-Bestimmung mit Glucose-Oxydase und Reoxydase. In: Methoden der Enzymatischen Analyse (Hrsg. H.U. Bergmeyer), S. 1172–1179. Weinheim: Verlag Chemie Weinheim 1970
Dulin, W.E., Gerritsen, G.C.: Summary of biochemical, physiological and morphological changes associated with diabetes in the Chinese hamster. Excerpta med. Int. Congr. Ser.172, 806–812 (1969)
Cooper, R.H., Ashcroft, S.J.H., Randle, P.J.: Concentration of adenosine 3′: 5′-cyclic monophosphate in mouse pancreatic islets measured by a protein-binding radioassay. Biochem. J.134, 599–605 (1973)
Rabinovitch, A., Gutzeit, A., Kikuchi, M., Cerasi, E., Renold, A.E.: Defective early phase insulin release in perifused isolated pancreatic islets of spiny mice (Acomys cahirinus). Diabetologia11, 457–465 (1975)
Grill, V., Asplund, K., Hellerström, G., Cerasi, E.: Decreased cyclic AMP and insulin response to glucose in isolated islets of neonatal rats. Diabetes24, 746–752 (1975)
Rabinovitch, A., Grill, V., Renold, A. E., Cerasi, E.: The relationship of insulin release to glucose-induced cyclic AMP accumulation in pancreatic islets of fed and starved rats. J. clin. Invest. (in press)
Rabinovitch, A., Gutzeit, A., Grill, V., Kikuchi, M., Renold, A.E., Cerasi, E.: Defective insulin secretion in the spiny mouse(Acomys cahirinus), possible value in the study of the pathophysiology of diabetes. Israel J. med. Sci.11, 730–737 (1975)
Boquist, L., Hellman, B., Lernmark, Å., Täljedal, I.-B.: Content of adenosine 3′: 5′ -cyclic monophosphate in the pancreatic islets of mice with a hereditary defect of insulin secretion. Biochem. biophys. Res. Commun.60, 1391–1396 (1974)
Kupiecki, F.P., Adams, L.D., Blanks, M.C., Gerritsen, G.C.: Insulin and glucagon release from perifused islets of Chinese hamsters that have a diabetic genotype but variable phenotype. Diabetes24 (Suppl. 2), 409 (1975)
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This work was presented in part at a meeting of the European Association for the Study of Diabetes, Sept. 1975, Munich, Germany
on leave from the Department of Endocrinology, Karolinska Hospital, Stockholm
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Rabinovitch, A., Renold, A.E. & Cerasi, E. Decreased cyclic AMP and Insulin responses to glucose in pancreatic islets of diabetic chinese hamsters. Diabetologia 12, 581–587 (1976). https://doi.org/10.1007/BF01220634
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DOI: https://doi.org/10.1007/BF01220634