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Insulin and glucagon levels in liver cirrhosis

Relationship with plasma amino acid imbalance of chronic hepatic encephalopathy

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Abstract

Alterations in insulin and glucagon levels migh account for the plasma amino acid imbalance of cirrhotics. In order to verify this hypothesis we evaluated basal insulin, glucagon, branched-chain amino acids, aromatic amino acids, and free tryptophan in 13 controls and 37 cirrhotics divided on the basis of their mental state; in 4 patients the hormonal and amino acid patterns were sequentially studied during various stages of encephalopathy. Glucagon is high in cirrhotics and progressively increases with the worsening of the mental state. Free tryptophan and aromatic amino acids show a similar behavior and significantly correlate with glucagon levels (r=0.67 and r=0.81, respectively). On the other hand insulin levels, which are high in cirrhotics without encephalopathy, fall in the presence of deep coma. Insulin did not correlated with any of the plasma amino acids considered. Our data suggest that the catabolic state associated with increased glucagon levels may account for some of the alterations in the plasma amino acid profiles of cirrhotics. Portal-systemic shunting does not seem to be the common cause of both hyperglucagonemia and hyperaminoacidemia. Decreased branched-chain amino acid levels may be related to factors different from those involved in the alterations of carbohydrate homeostasis.

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References

  1. Fischer JE, Yoshimura N, Aguirre A, James JH, Cumming MG, Abel RM, Deindoerfer F: Plasma amino acids in patients with hepatic encephalopathy. Am J Surg 127:40–47, 1974

    Google Scholar 

  2. Rosen MH, Yoshimura N, Hodgman BA, Fischer JE: Plasma amino acid pattern in hepatic encephalopathy of differing etiology. Gastroenterology 72:483–487, 1977

    Google Scholar 

  3. Cangiano L, Calcaterra V, Cascino A, Capocaccia L: Bound and free tryptophan plasma levels in hepatic encephalopathy. Rend Gastroenterol 8:186–189, 1976

    Google Scholar 

  4. Ono J, Hutson OG, Dombro RS, Levi JV, Livingstone A, Zeppa R: Tryptophan and hepatic coma. Gastroenterology 74:196–200, 1978

    Google Scholar 

  5. Cascino A, Cangiano C, Calcaterra V, Rossi-Fanelli F, Capocaccia L: Plasma amino acid imbalance in patients with liver disease. Am J Dig Dis 23:591–598, 1978

    Google Scholar 

  6. Soeters PB, Fischer JE: Insulin glucagon, amino acid imbalance, and hepatic encephalopathy. Lancet 2:880–882, 1976

    Google Scholar 

  7. Marco J, Diego J, Villanueva ML, Diaz-Fierros M, Valverde I, Segovia J: Elevated plasma glucagon levels in cirrhosis of the liver. N Engl J Med 289:1107–1111, 1973

    Google Scholar 

  8. Sherwin R, Joshi P, Hendler R, Felig P, Conn HO: Hyperglucagonemia in Laennec's cirrhosis. N Engl J Med 290:239–242, 1974

    Google Scholar 

  9. Collins JR, Crofford OB: Glucose intolerance and insulin resistance in patients with liver disease. Arch Intern Med 124:142–148, 1969

    Google Scholar 

  10. Marchesini G, Zoli M, Forlani G, Angiolini A, Bianchi FB, Pisi E: Glucagon levels and insulin/glucagon molar ratios in hepatic encephalopathy. Ital J Gastroenterol 10:193, 1978 (abstract)

    Google Scholar 

  11. Unger RH: Glucagon physiology and pathophysiology. N Engl J Med 285:443–449, 1971

    Google Scholar 

  12. Lam KC, Tall AR, Goldstein GB, Mistilis SP: Role of a false neurotransmitter, octopamine, in the pathogenesis of hepatic and renal encephalopathy. Scand J Gastroenterol 8:465–472, 1973

    Google Scholar 

  13. Aguilar-Parada E, Eisentraut AM, Unger RH: Pancreatic glucagon secretion in normal and diabetic subjects. Am J Med Sci 257:415–419, 1969

    Google Scholar 

  14. Muller WA, Faloona GR, Unger RH: The influence of the antecedent diet upon glucagon and insulin secretion. N Engl J Med 285:1450–1454, 1971

    Google Scholar 

  15. Denckla WD, Dewey HK: The determination of trytophan in plasma, liver and urine. J Lab Clin Med 69:160–169, 1967

    Google Scholar 

  16. Knell AJ, Davidson AR, William R, Kantamanemi BD, Curzon G: Dopamine and serotonine metabolism in hepatic encephalopathy. Br Med J 1:549–551, 1974

    Google Scholar 

  17. Morgan MY, Milsom JP, Sherlock S: Plama ratio of valine, leucine and isoleucine to phenylalanine and tyrosine in liver disease. Gut 19:1068–1073, 1978

    Google Scholar 

  18. Marchesini G, Forlani G, Angiolini A, Zoli M, Scolari MP, Bianchi FB, Pisi E: Oral glucose in cirrhotics: Effects on plasma aminoacid patterns and the role of insulin and glucagon. Diabete Metab, in press

  19. Marchesini G, Forlani G, Zoli M, Angiolini A, Bianchi FB, Pisi E: Influence of oral glucose on plasma glucagon levels and insulin/glucagon molar ratio in cirrhotics. Preliminary results. Ital J Gastroenterol 10:129–132, 1978

    Google Scholar 

  20. Johnston DG, Alberti KGMM, Faber OK, Binder C, Wright R: Hyperinsulinism of hepatic cirrhosis: Diminished degradation or hypersecretion? Lancet 1:10–12 1977

    Google Scholar 

  21. Chase RA, Sullivan S, Bloom SR, Silk DBA, Williams R: Insulin, glucagon and amino acid imbalance in fulminant hepatic failure. Gut 18:953, 1977 (abstract)

    Google Scholar 

  22. Adibi SH, Drash AL, Livi ED: Hormone and amino acid levels in altered nutritional states. J Lab Clin Med 76:722–732, 1970

    Google Scholar 

  23. Smith-Laing G, Sherlock S, Orskor H: Hyperglucagonemia of cirrhosis: A feature of hepatocellular damage. Ital J Gastroenterol 10:207, 1978 (abstract)

    Google Scholar 

  24. Sherwin RS, Fischer M, Bastl M, Hendler R, Black J, Finkelstein FO, Felig P: Decreased glucagon turnover: Mechanism of hyperglucagonemia and glucoses intolerance in uremia. Clin Res 23:332, 1975 (abstract)

    Google Scholar 

  25. Sherwin RS, Fischer M, Bessoff J, Snyder N, Hendler R, Conn HO, Felig P: Hyperglucagonemia in cirrhosis: Altered secretion and sensitivity to glucagon. Gastroenterology 74:1224–1228, 1978

    Google Scholar 

  26. Lipsett D, Madras BK, Wurtman RJ, Munro HN: Serum tryptophan level after carbohydrate ingestion: selective decline in non-albumin bound coincident with reduction in serum free fatty acids. Life Sci 12:57–64, 1973

    Google Scholar 

  27. Chiasson JL, Liljenquist JE, Sinclair-Smith BC, Lacy WW: Gluconeogenesis from alanine in normal postabsorbitive man: Intrahepatic stimulatory effect of glucagon. Diabetes 24:574–584, 1975

    Google Scholar 

  28. Mallette LE, Exton JH, Park GR: Control of gluconeogenesis from amino acids in the perfused rat liver. J Biol Chem 244:5713–5723, 1969

    Google Scholar 

  29. Wodside KH, Ward VF, Mortimore GE: Effect of glucagon on general protein degradation and synthesis in the perfused rat liver. J Biol Chem 249:5458–5463, 1974

    Google Scholar 

  30. Peterson RD, Beatty CH, Bocek RM: Effects of insulin and glucagon on carbohydrate and protein metabolism of adductor muscle and diaphragms. Endocrinology 72:71–77, 1963

    Google Scholar 

  31. Pozefsky T, Tancredi RG, Moxley RT, Dupre J, Tobin JD: Metabolism of forearm tissues in man. Studies with glucagon. Diabetes 25:128–135, 1976

    Google Scholar 

  32. Fitzpatrick GF, Meguid MM, Gilitz PH, Brennan MF: Glucagon infusion in normal man: Effects on 3-methylhistidine excretion and plasma amino acids. Metabolism 26:477–485, 1977

    Google Scholar 

  33. Soeters PB, Weir G, Ebeid AM, Fischer JE: Insulin, glucagon, portal systemic shunting, and hepatic failure in the dog. J Surg Res 23:183–188, 1977

    Google Scholar 

  34. Munro HN, Fernstrom JD, Wurtman RJ: Insulin, plasma amino acis imbalance and hepatic coma. Lancet 1:722–724, 1975

    Google Scholar 

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Authors and Affiliations

  1. Istituto di Nefrologia, Universitá di Bologna, Bologna, Italy

    Giulio Marchesini, Gabriele Forlani, Marco Zoli, Angela Angiolini, Maria P. Scolari, Francesco B. Bianchi & Emilio Pisi

  2. Istituto di Patologia Medica 1, Università di Bologna, Policlinico S. Orsola, 9, Via Massarenti, 40138, Bologna, Italy

    Giulio Marchesini, Gabriele Forlani, Marco Zoli, Angela Angiolini, Maria P. Scolari, Francesco B. Bianchi & Emilio Pisi

Authors
  1. Giulio Marchesini
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  2. Gabriele Forlani
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  3. Marco Zoli
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  4. Angela Angiolini
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  5. Maria P. Scolari
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  6. Francesco B. Bianchi
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  7. Emilio Pisi
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Marchesini, G., Forlani, G., Zoli, M. et al. Insulin and glucagon levels in liver cirrhosis. Digest Dis Sci 24, 594–601 (1979). https://doi.org/10.1007/BF01333703

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