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. 1987 Jan;79(1):20–24. doi: 10.1172/JCI112784

Relationship of glucagon suppression by insulin and somatostatin to the ambient glucose concentration.

A Starke, T Imamura, R H Unger
PMCID: PMC423975  PMID: 2878938

Abstract

The glucagon-suppressing activity of insulin and somatostatin were compared at high and low glucose concentrations. In normal dogs made hyperglucagonemic by phloridzin pretreatment, insulin and somatostatin suppressed glucagon at rates of 47 +/- 8 and 35 +/- 8%/h (NS), respectively, despite profound hypoglycemia. In severely hyperglycemic alloxan-diabetic dogs, insulin and somatostatin suppressed glucagon at rates of 48 +/- 13 and 54 +/- 6%/h, respectively, not different from the nondiabetic dogs. After phloridzin pretreatment to eliminate hyperglycemia in the diabetic dogs, insulin and somatostatin suppressed 51 +/- 8 and 31 +/- 10%/h (NS), respectively. Glucose infused in the phloridzin-pretreated insulin-deprived group suppressed glucagon only partially; insulin was required to reduce it further. We conclude that insulin and somatostatin suppress glucagon at similar rates irrespective of ambient glucose levels, and that diabetic hyperglucagonemia represents the summation of stimulation by insulin lack minus suppression by the associated hyperglycemia.

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Selected References

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

  1. Blazquez E., Muñoz-Barragan L., Patton G. S., Orci L., Dobbs R. E., Unger R. H. Gastric A-cell function in insulin-deprived depancreatized dogs. Endocrinology. 1976 Nov;99(5):1182–1188. doi: 10.1210/endo-99-5-1182. [DOI] [PubMed] [Google Scholar]
  2. Braaten J. T., Faloona G. R., Unger R. H. The effect of insulin on the alpha-cell response to hyperglycemia in long-standing alloxan diabetes. J Clin Invest. 1974 Apr;53(4):1017–1021. doi: 10.1172/JCI107638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buchanan K. D., Mawhinney W. A. Insulin control of glucagon release from insulin-deficient rat islets. Diabetes. 1973 Nov;22(11):801–803. doi: 10.2337/diab.22.11.801. [DOI] [PubMed] [Google Scholar]
  4. Gorus F. K., Malaisse W. J., Pipeleers D. G. Differences in glucose handling by pancreatic A- and B-cells. J Biol Chem. 1984 Jan 25;259(2):1196–1200. [PubMed] [Google Scholar]
  5. 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]
  6. Honey R. N., Fallon M. B., Weir G. C. Effects of exogenous insulin, glucagon, and somatostatin on islet hormone secretion in the perfused chicken pancreas. Metabolism. 1980 Dec;29(12):1242–1246. doi: 10.1016/0026-0495(80)90152-3. [DOI] [PubMed] [Google Scholar]
  7. Iversen J. Inhibition of pancreatic glucagon release by somatostatin: in vitro. Scand J Clin Lab Invest. 1974 Apr;33(2):125–129. [PubMed] [Google Scholar]
  8. Koerker D. J., Ruch W., Chideckel E., Palmer J., Goodner C. J., Ensinck J., Gale C. C. Somatostatin: hypothalamic inhibitor of the endocrine pancreas. Science. 1974 Apr 26;184(4135):482–484. doi: 10.1126/science.184.4135.482. [DOI] [PubMed] [Google Scholar]
  9. Matschinsky F. M., Pagliara A. S., Hover B. A., Pace C. S., Ferrendelli J. A., Williams A. Hormone secretion and glucose metabolism in islets of Langerhans of the isolated perfused pancreas from normal and streptozotocin diabetic rats. J Biol Chem. 1976 Oct 10;251(19):6053–6061. [PubMed] [Google Scholar]
  10. Mortimer C. H., Tunbridge W. M., Carr D., Yeomans L., Lind T., Coy D. H., Bloom S. R., Kastin A., Mallinson C. N., Besser G. M. Effects of growth-hormone release-inhibiting hormone on circulating glucagon, insulin, and growth hormone in normal, diabetic, acromegalic, and hypopituitary patients. Lancet. 1974 Apr 20;1(7860):697–701. doi: 10.1016/s0140-6736(74)92903-1. [DOI] [PubMed] [Google Scholar]
  11. Müller W. A., Faloona G. R., Unger R. H. Hyperglucagonemia in diabetic ketoacidosis. Its prevalence and significance. Am J Med. 1973 Jan;54(1):52–57. doi: 10.1016/0002-9343(73)90083-1. [DOI] [PubMed] [Google Scholar]
  12. Müller W. A., Faloona G. R., Unger R. H. The effect of experimental insulin deficiency on glucagon secretion. J Clin Invest. 1971 Sep;50(9):1992–1999. doi: 10.1172/JCI106691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ostenson C. G. Regulation of glucagon release: effects of insulin on the pancreatic A2-cell of the guinea pig. Diabetologia. 1979 Nov;17(5):325–330. doi: 10.1007/BF01235889. [DOI] [PubMed] [Google Scholar]
  14. Pagliara A. S., Stillings S. N., Haymond M. W., Hover B. A., Matschinsky F. M. Insulin and glucose as modulators of the amino acid-induced glucagon release in the isolated pancreas of alloxan and streptozotocin diabetic rats. J Clin Invest. 1975 Feb;55(2):244–255. doi: 10.1172/JCI107928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Raskin P., Fujita Y., Unger R. H. Effect of insulin-glucose infusions on plasma glucagon levels in fasting diabetics and nondiabetics. J Clin Invest. 1975 Nov;56(5):1132–1138. doi: 10.1172/JCI108188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Starke A., Grundy S., McGarry J. D., Unger R. H. Correction of hyperglycemia with phloridzin restores the glucagon response to glucose in insulin-deficient dogs: implications for human diabetes. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1544–1546. doi: 10.1073/pnas.82.5.1544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. UNGER R. H., EISENTRAUT A. M., McCALL M. S., MADISON L. L. Measurements of endogenous glucagon in plasma and the influence of blood glucose concentration upon its secretion. J Clin Invest. 1962 Apr;41:682–689. doi: 10.1172/JCI104525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Warne G. L., Alford F. P., Chisholm D. J., Court J. Glucagon and diabetes. II. Complete suppression of glucagon by insulin in human diabetes. Clin Endocrinol (Oxf) 1977 Apr;6(4):277–284. doi: 10.1111/j.1365-2265.1977.tb02012.x. [DOI] [PubMed] [Google Scholar]
  19. YALOW R. S., BERSON S. A. Immunoassay of endogenous plasma insulin in man. J Clin Invest. 1960 Jul;39:1157–1175. doi: 10.1172/JCI104130. [DOI] [PMC free article] [PubMed] [Google Scholar]

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