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. 1976 Nov;58(5):1209–1216. doi: 10.1172/JCI108574

Insulin release and cyclic AMP accumulation in response to glucose in pancreatic islets of fed and starved rats.

A Rabinovitch, V Grill, A E Renold, E Cerasi
PMCID: PMC333289  PMID: 186486

Abstract

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 of fed and starved rats. There was a preferential impairment of the early phase of glucose-induced insulin release in perifused islets of rats starved for 16 and 48 h. Similarly, the accumulation of 3H cyclic AMP in islets prelabeled with 3H-2-adenine was less in islets of 48 h starved than fed rats, during the first 10-min of stimulation with 26.7 mM glucose in the presence of 0.1 mM of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, whereas at 30 and 60 min 3H cyclic AMP responses to glucose were similar in fed and starved islets. Also, in 10-min incubations with glucose 3.3, 6.7, 10.0, 13.3, and 26.7 mM without and with 0.1 mM and 1.0 mM 3-isobutyl-1-methylxanthine, insulin release correlated strongly with the accumulation of 3H cyclic AMP in the islets of fed as well as starved rats. The thresholds for glucose-induced insulin and 3H cyclic AMP responses were higher and the maximal responses were lower in starved than fed islets. Preincubation of islets of 48-h starved rats with 16.7 mM glucose for 60 min corrected the impaired insulin and 3H cyclic AMP responses to glucose. Starvation-induced impairment of insulin secretory responses to glucose, and their restoration by preincubation with glucose in vitro, may represent acute regulatory effects of glucose on the adenylate cyclase-cyclic AMP system in the pancreatic beta cell.

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Selected References

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  1. Bosboom R. S., Zweens J., Bouman P. R. Effects of feeding and fasting on the insulin secretory response to glucose and sulfonylureas in intact rats and isolated perfused rat pancreas. Diabetologia. 1973 Aug;9(4):243–250. doi: 10.1007/BF01221849. [DOI] [PubMed] [Google Scholar]
  2. Buchanan K. D., Vance J. E., Williams R. H. Effect of starvation on insulin and glucagon release from isolated islets of Langerhans of the rat. Metabolism. 1969 Feb;18(2):155–162. doi: 10.1016/0026-0495(69)90110-3. [DOI] [PubMed] [Google Scholar]
  3. Cahill G. F., Jr, Herrera M. G., Morgan A. P., Soeldner J. S., Steinke J., Levy P. L., Reichard G. A., Jr, Kipnis D. M. Hormone-fuel interrelationships during fasting. J Clin Invest. 1966 Nov;45(11):1751–1769. doi: 10.1172/JCI105481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Capito 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. 1974 Sep;142(3):653–658. doi: 10.1042/bj1420653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Charles M. A., Fanska R., Schmid F. G., Forsham P. H., Grodsky G. M. Adenosine 3',5'-monophosphate in pancreatic islets: glucose-induced insulin release. Science. 1973 Feb 9;179(4073):569–571. doi: 10.1126/science.179.4073.569. [DOI] [PubMed] [Google Scholar]
  6. Fink G., Gutman R. A., Cresto J. C., Selawry H., Lavine R., Recant L. Glucose-induced insulin release patterns: effect of starvation. Diabetologia. 1974 Oct;10(5):421–425. doi: 10.1007/BF01221632. [DOI] [PubMed] [Google Scholar]
  7. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grey N. J., Goldring S., Kipnis D. M. The effect of fasting, diet, and actinomycin D on insulin secretion in the rat. J Clin Invest. 1970 May;49(5):881–889. doi: 10.1172/JCI106307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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 Jul 10;249(13):4196–4201. [PubMed] [Google Scholar]
  10. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  11. Hahn H. J., Fiedler H. Investigations on isolated islets in vitro. IX. Influence of food deprivation and glucose refeeding in vitro on insulin secretion. Acta Diabetol Lat. 1974 Nov-Dec;11(6):457–467. doi: 10.1007/BF02624585. [DOI] [PubMed] [Google Scholar]
  12. Hedeskov C. J., Capito K. The effect of starvation on insulin secretion and glucose metabolism in mouse pancreatic islets. Biochem J. 1974 Jun;140(3):423–433. doi: 10.1042/bj1400423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hellman B., Idahl L. A., Lernmark A., Täljedal I. B. The pancreatic beta-cell recognition of insulin secretagogues: does cyclic AMP mediate the effect of glucose? Proc Natl Acad Sci U S A. 1974 Sep;71(9):3405–3409. doi: 10.1073/pnas.71.9.3405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
  15. Howell S. L., Green I. C., Montague W. A possible role of adenylate cyclase in the long-tern dietary regulation of insulin secretion from rat islets of Langerhans. Biochem J. 1973 Oct;136(2):343–349. doi: 10.1042/bj1360343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Humes J. L., Rounbehler M., Kuehl F. A., Jr A new assay for measuring adenyl cyclase activity in intact cells. Anal Biochem. 1969 Nov;32(2):210–217. doi: 10.1016/0003-2697(69)90077-3. [DOI] [PubMed] [Google Scholar]
  17. Idahl L. A. Dynamics of pancreatic beta-cell responses to glucose. Diabetologia. 1973 Oct;9(5):403–412. doi: 10.1007/BF01239437. [DOI] [PubMed] [Google Scholar]
  18. 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. Diabetes. 1974 Jun;23(6):550–559. doi: 10.2337/diab.23.6.550. [DOI] [PubMed] [Google Scholar]
  19. Krishna G., Weiss B., Brodie B. B. A simple, sensitive method for the assay of adenyl cyclase. J Pharmacol Exp Ther. 1968 Oct;163(2):379–385. [PubMed] [Google Scholar]
  20. Kuo J. F., De Renzo E. C. A comparison of the effects of lipolytic and antilipolytic agents on adenosine 3',5'-monophosphate levels in adipose cells as determined by prior labeling with adenine-8-14C. J Biol Chem. 1969 May 10;244(9):2252–2260. [PubMed] [Google Scholar]
  21. Kuo W. N., Hodgins D. S., Kuo J. F. Regulation by various hormones and agents of adenosine-3',5'-monophosphate levels in islets of Langerhans of rats. Biochem Pharmacol. 1974 May 1;23(9):1387–1391. doi: 10.1016/0006-2952(74)90358-x. [DOI] [PubMed] [Google Scholar]
  22. Lacy P. E., Kostianovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes. 1967 Jan;16(1):35–39. doi: 10.2337/diab.16.1.35. [DOI] [PubMed] [Google Scholar]
  23. Levy J., Herchuelz A., Sener A., Malaisse W. J. The stimulus-secretion coupling of glucose-induced insulin release. XX. fasting: a model for altered glucose recognition by the B-cell. Metabolism. 1976 May;25(5):583–591. doi: 10.1016/0026-0495(76)90012-3. [DOI] [PubMed] [Google Scholar]
  24. Lopez-Quijada C., Gomez-Acebo J., Blazquez E. [Effect of starvation upon insulin secretion in the rabbit]. Acta Diabetol Lat. 1969 Oct-Dec;6(4):820–835. doi: 10.1007/BF01548088. [DOI] [PubMed] [Google Scholar]
  25. Malaisse W. J., Malaisse-Lagae F., Wright P. H. Effect of fasting upon insulin secretion in the rat. Am J Physiol. 1967 Oct;213(4):843–848. doi: 10.1152/ajplegacy.1967.213.4.843. [DOI] [PubMed] [Google Scholar]
  26. Malaisse W. J., Sener A., Levy J. The stimulus-secretion coupling of glucose-induced insulin release. Fasting-induced adaptation of key glycolytic enzymes in isolated islets. J Biol Chem. 1976 Mar 25;251(6):1731–1737. [PubMed] [Google Scholar]
  27. Matschinsky F. M., Ellerman J. E., Krzanowski J., Kotler-Brajtburg J., Landgraf R., Fertel R. The dual function of glucose in islets of Langerhans. J Biol Chem. 1971 Feb 25;246(4):1007–1011. [PubMed] [Google Scholar]
  28. Montague W., Cook J. R. The role of adenosine 3':5'-cyclic monophosphate in the regulation of insulin release by isolated rat islets of Langerhans. Biochem J. 1971 Mar;122(1):115–120. doi: 10.1042/bj1220115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Renold A. E. Insulin biosynthesis and secretion--a still unsettled topic. N Engl J Med. 1970 Jan 22;282(4):173–182. doi: 10.1056/NEJM197001222820401. [DOI] [PubMed] [Google Scholar]
  30. Scott D. A., Fisher A. M. THE INSULIN AND THE ZINC CONTENT OF NORMAL AND DIABETIC PANCREAS. J Clin Invest. 1938 Nov;17(6):725–728. doi: 10.1172/JCI101000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Selawry H., Gutman R., Fink G., Recant L. The effect of starvation on tissue adenosine 3'-5' monophosphate levels. Biochem Biophys Res Commun. 1973 Mar 5;51(1):198–204. doi: 10.1016/0006-291x(73)90528-7. [DOI] [PubMed] [Google Scholar]
  32. Solomon S. S., Ensinck J. W., Williams R. H. Effect of starvation on plasma immunoreactive insulin and non-suppressible insulin-like activity in normal and obese humans. Metabolism. 1968 Jun;17(6):528–534. doi: 10.1016/0026-0495(68)90045-0. [DOI] [PubMed] [Google Scholar]
  33. Turner D. S., Young D. A. The effect of fasting and selective re-feeding on insulin release in the rat. Acta Endocrinol (Copenh) 1973 Jan;72(1):46–53. doi: 10.1530/acta.0.0720046. [DOI] [PubMed] [Google Scholar]
  34. UNGER R. H., EISENTRAUT A. M., MADISON L. L. The effects of total starvation upon the levels of circulating glucagon and insulin in man. J Clin Invest. 1963 Jul;42:1031–1039. doi: 10.1172/JCI104788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Vance J. E., Buchanan K. D., Williams R. H. Effect of starvation and refeeding on serum immunoreactive glucagon and insulin levels. J Lab Clin Med. 1968 Aug;72(2):290–297. [PubMed] [Google Scholar]
  36. Voyles N., Gutman R. A., Selawry H., Fink G., Penhos J. C., Recant L. Interaction of various stimulators and inhibitors on insulin secretion in vitro. Horm Res. 1973;4(2):65–73. doi: 10.1159/000178291. [DOI] [PubMed] [Google Scholar]
  37. 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. Diabetologia. 1975 Jun;11(3):231–235. doi: 10.1007/BF00422327. [DOI] [PubMed] [Google Scholar]

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