Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1970 May;49(5):881–889. doi: 10.1172/JCI106307

The effect of fasting, diet, and actinomycin D on insulin secretion in the rat

N J Grey 1, S Goldring 1, D M Kipnis 1
PMCID: PMC535760  PMID: 5441542

Abstract

The present studies were performed to elucidate the mechanisms responsible for the impairment of glucose-stimulated insulin secretion observed in fasting. Rats fasted for 48 hr displayed marked impairment in their insulin secretory response to both oral and intravenous glucose. Glucose-stimulated insulin secretion was restored within 24 hr by refeeding; actinomycin D given before refeeding blocked the expected return of normal glucose-stimulated insulin secretion despite adequate food intake. Fasted rats refed a diet devoid of carbohydrate failed to display a return of normal insulin secretory responsiveness to oral glucose in contrast to rats fed isocalorically a high carbohydrate diet. Differences in insulin secretion in fed, fasted, and fasted-refed rats could not be attributed to changes in pancreatic insulin content. There was no significant difference in the insulin secretory response to aminophylline of fed, fasted, or fasted-refed rats. The intermittent pulsing of fasted rats with hyperglycemic episodes by the injection of small amounts of glucose (500 mg) intraperitoneally every 8 hr ameliorated the impairment of glucose-stimulated insulin secretion characteristic of the fasting state. These results suggest that the impairment of glucose-stimulated insulin secretion during fasting and its restoration by refeeding are regulated by changes in a glucose-inducible enzyme system in the pancreatic beta cell.

Full text

PDF
881

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashcroft S. J., Randle P. J. Glucose-6-phosphatase activity of mouse pancreatic islets. Nature. 1968 Aug 24;219(5156):857–858. doi: 10.1038/219857a0. [DOI] [PubMed] [Google Scholar]
  2. BECK P., KOUMANS J. H., WINTERLING C. A., STEIN M. F., DAUGHADAY W. H., KIPNIS D. M. STUDIES OF INSULIN AND GROWTH HORMONE SECRETION IN HUMAN OBESITY. J Lab Clin Med. 1964 Oct;64:654–667. [PubMed] [Google Scholar]
  3. BECK P., KOUMANS J. H., WINTERLING C. A., STEIN M. F., DAUGHADAY W. H., KIPNIS D. M. STUDIES OF INSULIN AND GROWTH HORMONE SECRETION IN HUMAN OBESITY. J Lab Clin Med. 1964 Oct;64:654–667. [PubMed] [Google Scholar]
  4. Boden G., Soeldner J. S., Gleason R. E., Marble A. Elevated serum human growth hormone and decreased serum insulin in prediabetic males after intravenous tolbutamide and glucose. J Clin Invest. 1968 Apr;47(4):729–739. doi: 10.1172/JCI105768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Coore H. G., Randle P. J. Regulation of insulin secretion studied with pieces of rabbit pancreas incubated in vitro. Biochem J. 1964 Oct;93(1):66–78. doi: 10.1042/bj0930066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Curry D. L., Bennett L. L., Grodsky G. M. Dynamics of insulin secretion by the perfused rat pancreas. Endocrinology. 1968 Sep;83(3):572–584. doi: 10.1210/endo-83-3-572. [DOI] [PubMed] [Google Scholar]
  8. ELRICK H., STIMMLER L., HLAD C. J., Jr, ARAI Y. PLASMA INSULIN RESPONSE TO ORAL AND INTRAVENOUS GLUCOSE ADMINISTRATION. J Clin Endocrinol Metab. 1964 Oct;24:1076–1082. doi: 10.1210/jcem-24-10-1076. [DOI] [PubMed] [Google Scholar]
  9. GRODSKY G. M., BATTS A. A., BENNETT L. L., VCELLA C., MCWILLIAMS N. B., SMITH D. F. EFFECTS OF CARBOHYDRATES ON SECRETION OF INSULIN FROM ISOLATED RAT PANCREAS. Am J Physiol. 1963 Oct;205:638–644. doi: 10.1152/ajplegacy.1963.205.4.638. [DOI] [PubMed] [Google Scholar]
  10. KARAM J. H., GRODSKY G. M., FORSHAM P. H. Excessive insulin response to glucose in obese subjects as measured by immunochemical assay. Diabetes. 1963 May-Jun;12:197–204. doi: 10.2337/diab.12.3.197. [DOI] [PubMed] [Google Scholar]
  11. KATZEN H. M., SODERMAN D. D., NITOWSKY H. M. KINETIC AND ELECTROPHORETIC EVIDENCE FOR MULTIPLE FORMS OF GLUCOSE-ATP PHOSPHOTRANSFERASE ACTIVITY FROM HUMAN CELL CULTURES AND RAT LIVER. Biochem Biophys Res Commun. 1965 Apr 23;19:377–382. doi: 10.1016/0006-291x(65)90472-9. [DOI] [PubMed] [Google Scholar]
  12. Katzen H. M. The multiple forms of mammalian hexokinase and their significance to the action of insulin. Adv Enzyme Regul. 1967;5:335–356. doi: 10.1016/0065-2571(67)90025-8. [DOI] [PubMed] [Google Scholar]
  13. Kipnis D. M. Insulin secretion in diabetes mellitus. Ann Intern Med. 1968 Nov;69(5):891–901. doi: 10.7326/0003-4819-69-5-891. [DOI] [PubMed] [Google Scholar]
  14. Luft R. Some considerations on the pathogenesis of diabetes mellitus. N Engl J Med. 1968 Nov 14;279(20):1086–1092. doi: 10.1056/NEJM196811142792005. [DOI] [PubMed] [Google Scholar]
  15. Malaisse W. J., Lemonnier D., Malaisse-Lagae F., Mandelbaum I. M. Secretion of and sensitivity to insulin in obese rats fed a high-fat diet. Horm Metab Res. 1969 Jan;1(1):9–13. doi: 10.1055/s-0028-1095167. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Matschinsky F. M., Ellerman J. E. Metabolism of glucose in the islets of Langerhans. J Biol Chem. 1968 May 25;243(10):2730–2736. [PubMed] [Google Scholar]
  18. Owen O. E., Felig P., Morgan A. P., Wahren J., Cahill G. F., Jr Liver and kidney metabolism during prolonged starvation. J Clin Invest. 1969 Mar;48(3):574–583. doi: 10.1172/JCI106016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Perley M. J., Kipnis D. M. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic sujbjects. J Clin Invest. 1967 Dec;46(12):1954–1962. doi: 10.1172/JCI105685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Perley M., Kipnis D. M. Plasma insulin responses to glucose and tolbutamide of normal weight and obese diabetic and nondiabetic subjects. Diabetes. 1966 Dec;15(12):867–874. doi: 10.2337/diab.15.12.867. [DOI] [PubMed] [Google Scholar]
  21. RABINOWITZ D., ZIERLER K. L. Forearm metabolism in obesity and its response to intra-arterial insulin. Characterization of insulin resistance and evidence for adaptive hyperinsulinism. J Clin Invest. 1962 Dec;41:2173–2181. doi: 10.1172/JCI104676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sharma C., Manjeshwar R., Weinhouse S. Hormonal and dietary regulation of hepatic glucokinase. Adv Enzyme Regul. 1964;2:189–200. doi: 10.1016/s0065-2571(64)80013-3. [DOI] [PubMed] [Google Scholar]
  23. Sols A., Salas M., Viñuela E. Induced biosynthesis of liver glucokinase. Adv Enzyme Regul. 1964;2:177–188. doi: 10.1016/s0065-2571(64)80012-1. [DOI] [PubMed] [Google Scholar]
  24. Turtle J. R., Littleton G. K., Kipnis D. M. Stimulation of insulin secretion by theophylline. Nature. 1967 Feb 18;213(5077):727–728. doi: 10.1038/213727a0. [DOI] [PubMed] [Google Scholar]
  25. VINUELA E., SALAS M., SOLS A. Glucokinase and hexokinase in liver in relation to glycogen synthesis. J Biol Chem. 1963 Mar;238:1175–1177. [PubMed] [Google Scholar]
  26. WILLIAMSON J. R., LACY P. E., GRISHAM J. W. Ultrastructural changes in islets of the rat produced by tolbutamide. Diabetes. 1961 Nov-Dec;10:460–469. doi: 10.2337/diab.10.6.460. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES