Effect of Diamide and Reduced Glutathione on the Elevated Levels of Cyclic AMP in Rat Pancreatic Islets Exposed to Glucose, P-chloromercuribenzoate and Aminophylline

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1982 Jun 1

PMID 6287310

Citations 1

Authors

H P Ammon

S Heinzl

M Abdel-Hamid

H M Kallenberger

I Hagenloh

Affiliations

Soon will be listed here.

Abstract

In rat pancreatic islets the effects of diamide, which has been shown to decrease islet levels of reduced glutathione (GSH), and of exogenous GSH were investigated on cyclic AMP as increased by glucose, p-chloromercuribenzoate, and aminophylline. In addition the effect of diamide on islet ATP level, low Km and high Km phosphodiesterases was studied. Diamide (0.1 mM) inhibited the increase of cyclic AMP (cAMP) in response to glucose (16.7 mM), and p-chloro-mercuribenzoate (1 mM) in the presence of 5.6 mM glucose. No inhibitory effect of diamide could be demonstrated when cAMP was raised by 10 mM aminophylline in the presence of 5.6 mM glucose. The glucose (27.7 mM) stimulated increase of cAMP was further augmented by GSH (0.4 mM) whereas GSH in the presence of 5.6 mM glucose had no such effect. Diamide neither affected islet high Km nor low Km cAMP-phosphodiesterases. Diamide (0.1 mM) as used in this study did not affect islet AMP levels. A concentration dependent decrease of ATP was observed, however, with higher concentrations of diamide (0.25, 0.5 and 1.0 mM). It is suggested that the accumulation of islet cAMP in response to glucose and para-chloromercuribenzoate depends on the redox state of islet thiols. Since thiol oxidant diamide neither affected cAMP-phosphodiesterase activities nor inhibited aminophylline induced accumulation of cAMP in the presence of low glucose the possibility is raised that in pancreatic islets the formation of cAMP rather than its degradation depends on the redox state of islet thiols.

Citing Articles

Arginine Thiazolidine Carboxylate Stimulates Insulin Secretion through Production of Ca2+-Mobilizing Second Messengers NAADP and cADPR in Pancreatic Islets.

Park D, Shawl A, Ha T, Park K, Kim S, Kim U PLoS One. 2015; 10(8):e0134962.

PMID: 26247205 PMC: 4527757. DOI: 10.1371/journal.pone.0134962.

References

Ammon H, Verspohl E . Pyridine nucleotides in pancreatic islets during inhibition of insulin release by exogenous insulin. Endocrinology. 1976; 99(6):1469-76. DOI: 10.1210/endo-99-6-1469. View

Claro A, Grill V, Efendic S, Luft R . Studies on the mechanisms of somatostatin action on insulin release. IV. effect of somatostatin on cyclic AMP levels and phosphodiesterase activity in isolated rat pancreatic islets. Acta Endocrinol (Copenh). 1977; 85(2):379-88. View

Ammon H, Akhtar M, NIKLAS H, HEGNER D . Inhibition of p-chloromercuribenzoate- and glucose-induced insulin release in vitro by methylene blue, diamide, and tert-butyl hydroperoxide. Mol Pharmacol. 1977; 13(4):598-605. View

Hellman B, Idahl L, Lernmark A, Sehlin J, Taljedal I . Role of thiol groups in insulin release: studies with poorly permeating disulphides. Mol Pharmacol. 1973; 9(6):792-801. View

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. 1974; 249(13):4196-201. View

Zawalich W, KARL R, Ferrendelli J, Matschinsky F . Factors governing glucose induced elevation of cyclic 3'5' AMP levels in pancreatic islets. Diabetologia. 1975; 11(3):231-5. DOI: 10.1007/BF00422327. View

Ammon H, Abdel-Hamid M . Potentiation of the insulin-releasing capacity of tolbutamide by thiols: studies on the isolated perfused pancreas. Naunyn Schmiedebergs Arch Pharmacol. 1981; 317(3):262-7. DOI: 10.1007/BF00503828. View

Johnson R, Hardman J, Broadus A, SUTHERLAND E . Analysis of adenosine 3',5'-monophosphate with luciferase luminescence. Anal Biochem. 1970; 35(1):91-7. DOI: 10.1016/0003-2697(70)90014-x. View

KISSANE J, Robins E . The fluorometric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J Biol Chem. 1958; 233(1):184-8. View

10.

Storm D, Dolginow Y . Glucagon stimulation of adenylate cyclase sulfhydryl reactivity. Evidence for hormone-induced conformational changes. J Biol Chem. 1973; 248(14):5208-10. View

11.

Kosower N, Kosower E, Wertheim B, Correa W . Diamide, a new reagent for the intracellular oxidation of glutathione to the disulfide. Biochem Biophys Res Commun. 1969; 37(4):593-6. DOI: 10.1016/0006-291x(69)90850-x. View

12.

BLOOM G, Hellman B, Idahl L, Lernmark A, Sehlin J, Taljedal I . Effects of organic mercurials on mammalian pancreatic -cells. Insulin release, glucose transport, glucose oxidation, membrane permeability and ultrastructure. Biochem J. 1972; 129(2):241-54. PMC: 1174074. DOI: 10.1042/bj1290241. View

13.

Malaisse W, Malaisse-Lagae F, Mayhew D . A possible role for the adenylcyclase system in insulin secretion. J Clin Invest. 1967; 46(11):1724-34. PMC: 292923. DOI: 10.1172/JCI105663. View

14.

Lambert A, Kanazawa Y, Burr I, Orci L, Renold A . On the role of cyclic AMP in insulin release: I. Overall effects in cultured fetal rat pancreas. Ann N Y Acad Sci. 1971; 185:232-44. DOI: 10.1111/j.1749-6632.1971.tb45252.x. View

15.

Storm D, Gunsalus R . Methylmercury is a potent inhibitor of membrane adenyl cyclase. Nature. 1974; 250(5469):778-9. DOI: 10.1038/250778a0. View

16.

Mukherjee S, Lynn W . Reduced nicotinamide adenine dinucleotide phosphate oxidase in adipocyte plasma membrane and its activation by insulin. Possible role in the hormone's effects on adenylate cyclase and the hexose monophosphate shunt. Arch Biochem Biophys. 1977; 184(1):69-76. DOI: 10.1016/0003-9861(77)90327-7. View

17.

Mukherjee S, Lynn W . Role of cellular redox state and glutathione in adenylate cyclase activity in rat adipocytes. Biochim Biophys Acta. 1979; 568(1):224-33. DOI: 10.1016/0005-2744(79)90289-4. View

18.

Baba A, Lee E, Matsuda T, Kihara T, Iwata H . Reversible inhibition of adenylate cyclase activity of rat brain caudate nucleus by oxidized glutathione. Biochem Biophys Res Commun. 1978; 85(3):1204-10. DOI: 10.1016/0006-291x(78)90670-8. View

19.

Grill V, Cerasi E . Interacting effects of sulfonylureas and glucose on cyclic AMP metabolism and insulin release in pancreatic islets of the rat. J Clin Invest. 1978; 61(5):1346-54. PMC: 372657. DOI: 10.1172/JCI109052. View

20.

Hellman B, Idahl L, Lernmark A, Taljedal I . The pancreatic beta-cell recognition of insulin secretagogues: does cyclic AMP mediate the effect of glucose?. Proc Natl Acad Sci U S A. 1974; 71(9):3405-9. PMC: 433781. DOI: 10.1073/pnas.71.9.3405. View