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. 1979 Oct;20(10):817–824. doi: 10.1136/gut.20.10.817

Effect of portasystemic venous shunt surgery on hyperglucagonaemia in cirrhosis: paired studies of pre- and post-shunted subjects

F J Dudley, F P Alford, D J Chisholm, D M Findlay
PMCID: PMC1412721  PMID: 533693

Abstract

The effect of liver disease on glucagon metabolism was examined in nine patients with chronic liver disease who were studied both before and after the creation of a surgical portasystemic shunt. Hepatocellular function did not deteriorate after shunt surgery. However, hepatic perfusion with splanchnic venous blood, as determined by scintisplenoportography, decreased after shunt surgery in six subjects but appeared unaltered in three. Basal plasma immunoreactive glucagon (IRG) levels in the pre-shunt cirrhotic group were significantly greater (p <0·005) than in control subjects and further increased (p <0·05) after shunt surgery. Moreover, the increase in basal IRG after shunt was evident only in patients in whom portasystemic shunting was demonstrably increased by surgery. Despite the higher basal IRG levels postoperatively, shunt surgery in the cirrhotics did not alter basal glucose and insulin levels or the glucose and insulin response to a glucose or protein load. Circulating IRG was heterogeneous in the pre-shunt cirrhotic patients: the 9000 molecular weight fraction comprised 27±4%, the 3500 mol. wt. fraction 71±4%, and the > 40 000 mol. wt. fraction was minimal. After shunt surgery, the relative proportion of the 9000 mol. wt. fraction of IRG (13±3%) decreased significantly (p <0·05) and this fall was associated with a corresponding increase in the 3,500 mol. wt. fraction (84±4%). It is concluded that, in cirrhosis, hyperglucagonaemia is: (1) dependent on the degree of portasystemic shunting rather than impaired hepatocellular function; (2) predominantly due to increased circulating 3500 molecular weight glucagon; and (3) not a major factor in the pathogenesis of carbohydrate intolerance in liver disease.

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Selected References

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

  1. Albano J. D., Ekins R. P., Maritz G., Turner R. C. A sensitive, precise radioimmunoassay of serum insulin relying on charcoal separation of bound and free hormone moieties. Acta Endocrinol (Copenh) 1972 Jul;70(3):487–509. doi: 10.1530/acta.0.0700487. [DOI] [PubMed] [Google Scholar]
  2. Alford F. P., Bloodm S. R., Nabarro J. D. Glucagon levels in normal and diabetic subjects: use of a specific immunoabsorbent for glucagon radioimmunoassay. Diabetologia. 1977 Jan;13(1):1–6. doi: 10.1007/BF00996319. [DOI] [PubMed] [Google Scholar]
  3. Alford F. P., Bloom S. R., Nabarro J. D. Glucagon metabolism in man, studies on the metabolic clearance rate and the plasma acute disappearance time of glucagon in normal and diabetic subjects. J Clin Endocrinol Metab. 1976 May;42(5):830–838. doi: 10.1210/jcem-42-5-830. [DOI] [PubMed] [Google Scholar]
  4. BRODIE B. B., AXELROD J. The estimation of antipyrine in biological materials. J Biol Chem. 1949 May;179(1):25–29. [PubMed] [Google Scholar]
  5. Branch R. A., Herbert C. M., Read A. E. Determinants of serum antipyrine half-lives in patients with liver disease. Gut. 1973 Jul;14(7):569–573. doi: 10.1136/gut.14.7.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chisholm D. J., Alford F. P., Harewood M. S., Findlay D. M., Gray B. N. Nature and biologic activity of "extrapancreatic glucagon": studies in pancreatectomized cats. Metabolism. 1978 Mar;27(3):261–273. doi: 10.1016/0026-0495(78)90106-3. [DOI] [PubMed] [Google Scholar]
  7. Davies T. F., Prudhoe K., Douglas A. P. Plasma cyclic adenosine-3', 5'-monophosphate response to glucagon in patients with liver disease. Br Med J. 1976 Apr 17;1(6015):931–933. doi: 10.1136/bmj.1.6015.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drapanas T. Interposition mesocaval shunt for treatment of portal hypertension. Ann Surg. 1972 Oct;176(4):435–448. doi: 10.1097/00000658-197210000-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dudley F. J., Wong C. L., Dugdale L. M. Demonstration of surgical portasystemic venous shunts by scintisplenoportography. Aust N Z J Med. 1977 Oct;7(5):511–514. doi: 10.1111/j.1445-5994.1977.tb03373.x. [DOI] [PubMed] [Google Scholar]
  10. Exton J. H., Lewis S. B., Ho R. J., Robison G. A., Park C. R. The role of cyclic AMP in the interaction of glucagon and insulin in the control of liver metabolism. Ann N Y Acad Sci. 1971 Dec 30;185:85–100. doi: 10.1111/j.1749-6632.1971.tb45239.x. [DOI] [PubMed] [Google Scholar]
  11. Felig P., Wahren J., Sherwin R., Hendler R. Insulin, glucagon, and somatostatin in normal physiology and diabetes mellitus. Diabetes. 1976 Dec;25(12):1091–1099. doi: 10.2337/diab.25.12.1091. [DOI] [PubMed] [Google Scholar]
  12. Gochman N., Schmitz J. M. Application of a new peroxide indicator reaction to the specific, automated determination of glucose with glucose oxidase. Clin Chem. 1972 Sep;18(9):943–950. [PubMed] [Google Scholar]
  13. Harman A. W., Penhall R. K., Priestly B. G., Frewin D. B., Phillips P. J., Clarkson A. R. Salivary antipyrine kinetics in hepatic and renal disease and in patients on anticonvulsant therapy. Aust N Z J Med. 1977 Aug;7(4):385–390. doi: 10.1111/j.1445-5994.1977.tb04401.x. [DOI] [PubMed] [Google Scholar]
  14. Jaspan J. B., Rubenstein A. H. Circulating glucagon. Plasma profiles and metabolism in health and disease. Diabetes. 1977 Sep;26(9):887–904. doi: 10.2337/diab.26.9.887. [DOI] [PubMed] [Google Scholar]
  15. Kashiwagi T., Kamada T., Abe H. Dynamic studies on the portal hemodynamics by scintiphotosplenoportography: the visualization of portal venous system using 99mTc. Gastroenterology. 1974 Oct;67(4):668–673. [PubMed] [Google Scholar]
  16. Kuku S. F., Zeidler A., Emmanouel D. S., Katz A. I., Rubenstein A. H. Heterogeneity of plasma glucagon: patterns in patients with chronic renal failure and diabetes. J Clin Endocrinol Metab. 1976 Jan;42(1):173–176. doi: 10.1210/jcem-42-1-173. [DOI] [PubMed] [Google Scholar]
  17. Marco J., Diego J., Villanueva M. L., Diaz-Fierros M., Valverde I., Segovia J. M. Elevated plasma glucagon levels in cirrhosis of the liver. N Engl J Med. 1973 Nov 22;289(21):1107–1111. doi: 10.1056/NEJM197311222892103. [DOI] [PubMed] [Google Scholar]
  18. REYNOLDS T. B., MIKKELSEN W. P., REDEKERAG, YAMAHIRO H. S. The effect of a side-to-side portacaval shunt on hepatic hemodynamics in cirrhosis. J Clin Invest. 1962 Jun;41:1242–1248. doi: 10.1172/JCI104586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sherwin R. S., Fisher M., Bessoff J., Snyder N., Hendler R., Conn H. O., Felig P. Hyperglucagonemia in cirrhosis: altered secretion and sensitivity to glucagon. Gastroenterology. 1978 Jun;74(6):1224–1228. [PubMed] [Google Scholar]
  20. Sherwin R., Joshi P., Hendler R., Felig P., Conn H. O. Hyperglucagonemia in Laennec's cirrhosis. The role of portal-systemic shunting. N Engl J Med. 1974 Jan 31;290(5):239–242. doi: 10.1056/NEJM197401312900502. [DOI] [PubMed] [Google Scholar]
  21. Valverde I., Dobbs R., Unger R. H. Heterogeneity of plasma glucagon immunoreactivity in normal, depancreatized, and alloxan-diabetic dogs. Metabolism. 1975 Sep;24(9):1021–1028. doi: 10.1016/0026-0495(75)90095-5. [DOI] [PubMed] [Google Scholar]
  22. Valverde I., Villanueva M. L. Heterogeneity of plasma immunoreactive glucagon. Metabolism. 1976 Nov;25(11 Suppl 1):1393–1395. doi: 10.1016/s0026-0495(76)80149-7. [DOI] [PubMed] [Google Scholar]
  23. Warren W. D., Zeppa R., Fomon J. J. Selective trans-splenic decompression of gastroesophageal varices by distal splenorenal shunt. Ann Surg. 1967 Sep;166(3):437–455. doi: 10.1097/00000658-196709000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Weir G. C., Knowlton S. D., Martin D. B. High molecular weight glucagon-like immunoreactivity in plasma. J Clin Endocrinol Metab. 1975 Feb;40(2):296–302. doi: 10.1210/jcem-40-2-296. [DOI] [PubMed] [Google Scholar]

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