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Possible roles of insulin, glucagon, growth hormone and free fatty acids in the pathogenesis of insulin resistance of subjects with chronic liver diseases

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Summary

In the present investigation, insulin sensitivity and fasting levels of insulin, C-peptide, glucagon, growth hormone and free fatty acids were estimated and correlated in a population of individuals suffering from liver cirrhosis or chronic hepatitis. Insulin sensitivity, assessed by glucose disappearance rate after intravenous bolus injection of insulin, was reduced but not significantly different from controls in subjects with chronic persistent hepatitis, while it was significantly reduced in individuals suffering from chronic active hepatitis or liver cirrhosis. Insulin, glucagon, growth hormone, and free fatty acid fasting levels were higher than in healthy subjects in individuals with liver cirrhosis or chronic active hepatitis but not in subjects with chronic persistent hepatitis. C-peptide concentrations did not differ from controls in subjects with liver disease. Significant negative correlations occurred between coefficients of insulin sensitivity and fasting concentrations of insulin, glucagon, growth hormone and free fatty acids, but not with fasting levels of C-peptide. Positive relationships were present between fasting levels of free fatty acids and both glucagon and growth hormone concentrations. These results show that, unlike subjects with liver cirrhosis and chronic active hepatitis, individuals suffering from chronic persistent hepatitis do not differ from healthy subjects in insulin sensitivity and fasting levels of insulin, glucagon, growth hormone, and free fatty acids. Moreover, they suggest that both hyperinsulinemia and high concentrations of counterregulatory substances might play a role in the pathogenesis of insulin resistance in subjects suffering from chronic liver disease.

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References

  1. Alberti K. G. M. M., Record C. O., Williamson D. H., Wright R.: Metabolic changes in active chronic hepatitis — Clin. Sci.42, 591, 1972.

    PubMed  CAS  Google Scholar 

  2. Becker M., Cook G. C., Wright A. D.: Paradoxical elevation of growth hormone in active chronic hepatitis — Lancet.ii, 1035, 1969.

    Article  Google Scholar 

  3. Berkowitz D.: Glucose tolerance, free fatty acids and serum insulin responses in patients with cirrhosis — Amer. J. digest. Dis.14, 691, 1969.

    Article  CAS  Google Scholar 

  4. Boden G., Soeldner J. S.: A sensitive double antibody radioimmunoassay for HGH: levels of serum HGH following rapid tolbutamide infusion — Diabetologia3, 413, 1967.

    Article  PubMed  CAS  Google Scholar 

  5. Bonora E., Coscelli C., Orioli S., Cambi R., Buzzelli G., Gentilini P., Butturini U.: Hyperinsulinemia of chronic active hepatitis: impaired insulin removal rather than pancreatic hypersecretion — Hormone metab. Res.16, 111, 1984.

    CAS  Google Scholar 

  6. Buzzelli G., Bonora E., Coscelli C., Orioli S., Cambi R., Butturini U., Gentilini P.: Secretion and hepatic removal of insulin in active chronic hepatitis — Diabetologia23, 159, 1982.

    Google Scholar 

  7. Buzzelli G., Bonora E., Coscelli C., Orioli S., Smorlesi C., Butturini U., Gentlini P.: Glucose intolerance in chronic active hepatitis. In:Langer M., Chiandussi L., Chopra I. J., Martini L. (Eds): The endocrines and the liver. Academic Press, London-New York, 1982; p. 355.

    Google Scholar 

  8. Cameron D. P., Burger H. G., Catt K. J., Gordon E., Watts J. M. K.: Metabolic clearance of human growth hormone in patients with hepatic and renal failure and in the isolated perfused pig liver — Metabolism21, 895, 1972.

    Article  PubMed  CAS  Google Scholar 

  9. Collins J. R., Lacy W. W., Stiel J. N., Crofford O. B.: Glucose intolerance and insulin resistance in patients with liver disease. II. A study of etiologic factors and evaluation of insulin actions — Arch. intern. Med.126, 608, 1970.

    Article  PubMed  CAS  Google Scholar 

  10. Conn H. O., Daughaday W. H.: Cirrhosis and diabetes. V. Serum human growth hormone levels in Laënnec’s cirrhosis — J. Lab. clin. Med.76, 678, 1970.

    PubMed  CAS  Google Scholar 

  11. Conn H. O., Schreiber W., Elkington S. G., Johnston T. R.: Cirrhosis and diabetes. I. Increased incidence of diabetes in patients with Laënnec’s cirrhosis — Amer. J. digest. Dis.14, 837, 1969.

    Article  CAS  Google Scholar 

  12. Fain J. N., Dodd A., Novak L.: Relationship of protein synthesis and cyclic AMP to lipolytic action of growth hormone and glucocorticoids — Metabolism20, 109, 1971.

    Article  PubMed  CAS  Google Scholar 

  13. Fain J. N., Kovacev V. P., Scow R. O.: Effect of growth hormone and desamethazone on lipolysis and metabolism in isolated fat cells of the rat — J. biol. Chem.240, 3522, 1965.

    PubMed  CAS  Google Scholar 

  14. Ferrannini E., Barret E., Bevilacqua S., DeFronzo R. A.: Effect of fatty acids on glucose production and utilization in man — J. clin. Invest.72, 1737, 1983.

    PubMed  CAS  Google Scholar 

  15. Fujita S., Takimoto T., Kobayashi M., Shigeta Y., Hoshi M.: Erythrocyte insulin receptors in patients with chronic liver diseases — Hormone metab. Res.14, 51, 1982.

    CAS  Google Scholar 

  16. Greco A. V., Bertoli A., Ghirlanda G., Manna R., Altomonte L., Rebuzzi A. G.: Insulin resistance in liver cirrhosis: decreased insulin binding to circulating monocytes — Hormone metab. Res.12, 577, 1980.

    CAS  Google Scholar 

  17. Greco A. V., Crucitti F., Ghirlanda G., Manna R., Altomonte L., Rebuzzi A. G., Bertoli A.: Insulin and glucagon concentrations in portal and peripheral veins in patients with hepatic cirrhosis — Diabetologia17, 23, 1979.

    Article  PubMed  CAS  Google Scholar 

  18. Greco A. V., Ghirlanda G., Patrono C., Fedeli G., Manna R.: Behavior of pancreatic glucagon, insulin, and HGH in liver cirrhosis, after arginine and i.v. glucose — Acta diabetol. lat.11, 330, 1974.

    Article  PubMed  CAS  Google Scholar 

  19. Greco A. V., Rebuzzi A. G., Altomonte L., Manna R., Bertoli A., Ghirlanda G.: Glucose, insulin, and somatostatin infusion for the determination of insulin resistance in liver cirrhosis — Hormone metab. Res.11, 547, 1979.

    CAS  Google Scholar 

  20. Gunnlaugsson O., Berkowitz D.: Individual free fatty acids in patients with liver disease — Digest. Dis. Sci.22, 1005, 1977.

    Article  CAS  Google Scholar 

  21. Hales C. N., Randle P. J.: Immunoassay of insulin with insulin-antibody precipitate — Biochem. J.83, 137, 1963.

    Google Scholar 

  22. Henquin J. C., Malvaux P., Lambert A. E.: Glucagon immunoassay using polyethylene glycol to precipitate antibody-bound hormone — Diabetologia10, 61, 1974.

    Article  PubMed  CAS  Google Scholar 

  23. Hernandez A., Zorrilla E., Gershberg H.: Decreased insulin production, elevated growth hormone levels and glucose intolerance in liver disease — J. Lab. clin. Med.73, 25, 1969.

    PubMed  CAS  Google Scholar 

  24. Johnston D. G., Alberti K. G. M. M., Binder C., Faber O. K., Wright R., Ørskov H.: Hormonal and metabolic changes in hepatic cirrhosis — Hormone metab. Res.14, 34, 1982.

    Article  CAS  Google Scholar 

  25. Johnston D. G., Alberti K. G. M. M., Faber O. K., Binder C., Wright R.: Hyperinsulinism of hepatic cirrhosis: diminished degradation or hypersecretion? — Lancetii, 10, 1977.

    Article  Google Scholar 

  26. Kaneko T., Oka H., Munemura M., Oda T., Yamashita K., Suzuki S., Yanaihara N., Hashimoto T., Yanaihara C.: Radioimmunoassay of human proinsulin C-peptide using synthetic human connecting peptide — Endocrinol. Jap.21, 141, 1974.

    CAS  Google Scholar 

  27. Leevy C. M., Popper H., Sherlock S.: Hepatitis, fibrosis, and cirrhosis. Standardization of nomenclature, diagnostic criteria and diagnostic methodology for diseases of the liver and biliary tract. In:Leevy G. M., Tygstrup N. (Eds): Diseases of the liver and biliary tract. S. Karger, Basel, 1976; p. 2.

    Google Scholar 

  28. Liljenquist J. E., Bomboy J. D., Lewis S. B., Sinclair-Surith B. C., Felts P. W., Lacy W. W., Crofford O. B., Liddle G. W.: Effects of glucagon on lipolysis and ketogenesis in normal and diabetic man — J. clin. Invest.53, 190, 1974.

    PubMed  CAS  Google Scholar 

  29. Maloff B. L., Levine J. H. H., Lockwood D. H.: Direct effects of growth hormone on insulin action in rat adipose tissue maintainedin vitro — Endocrinology107, 538, 1980.

    PubMed  CAS  Google Scholar 

  30. Marco J., Diego J., Villanueva M. L., Diaz-Fierros M., Valverde I., Segovia J. M.: Elevated plasma glucagon levels in cirrhosis of the liver — New Engl. J. Med.289, 1107, 1973.

    Article  PubMed  CAS  Google Scholar 

  31. McCann V. J., Fulton T. T.: Cortisol metabolism in chronic liver disease — J. clin. Endocrinol.40, 1038, 1975.

    CAS  Google Scholar 

  32. Megyesi C., Samols E., Marks V.: Glucose tolerance and diabetes in chronic liver disease — Lancetii, 1051, 1967.

    Article  Google Scholar 

  33. Mortiaux A., Dawson A. M.: Plasma free fatty acids in liver disease — Gut2, 304, 1960.

    Google Scholar 

  34. Nome A., Okabe H., Kita M.: A new colorimetric micro-determination of free fatty acids in serum — Clin. chim. Acta43, 317, 1973.

    Article  Google Scholar 

  35. Owens D., Srivastava M. C., Tompkins C. V., Nabarro J. D. N., Sønksen P. H.: Studies of the metabolic clearance rate, apparent distribution space, and plasma half-disappearance time of unlabelled human growth hormone in normal subjects and in patients with liver disease, renal disease, thyroid disease and diabetes mellitus — Europ. J. clin. Invest.3, 284, 1973.

    Article  PubMed  CAS  Google Scholar 

  36. Perez G., Trimarco B., Ungaro B., Rengo F., Saccà L.: Glucoregulatory response to insulin-induced hypoglycemia in Laënnec’s cirrhosis — J. clin. Endocrinol.46, 778, 1978.

    CAS  Google Scholar 

  37. Portugal-Alvarez J., Perezagua Clamagirand C., Souto J. M., Catalán E., Vila T., Velasco-Martín A.: Relationship between growth hormone, insulin, and urinary oestrogens in hepatic cirrhosis — Acta diabetol. lat.11, 1, 1974.

    Article  PubMed  Google Scholar 

  38. Proietto J., Alford F. P., Dudley F. J.: The mechanism of the carbohydrate intolerance of cirrhosis — J. clin. Endocrinol.55, 1030, 1980.

    Google Scholar 

  39. Randle P. J., Garland P. B., Hales C. N., Newsholme E. A.: The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbance of diabetes mellitus — Lanceti, 785, 1963.

    Article  Google Scholar 

  40. Riggio O., Merli M., Cangiano C., Capocaccia R., Cascino A., Lala A., Leonetti F., Mauceri M., Pepe M., Rossi Fanelli F., Savioli M., Tamburrano G., Capocaccia L.: Glucose intolerance in liver cirrhosis — Metabolism31, 627, 1982.

    Article  PubMed  CAS  Google Scholar 

  41. Samaan N. A., Stone D. B., Eckhardt R. D.: Serum glucose, insulin, and growth hormone in chronic hepatic cirrhosis — Arch. intern. Med.124, 149, 1969.

    Article  PubMed  CAS  Google Scholar 

  42. Schade D. S., Eaton R. P.: Modulation of fatty acids metabolism by glucagon in man. I. Effects in normal subjects — Diabetes24, 510, 1975.

    Article  PubMed  CAS  Google Scholar 

  43. 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 — Gastroenterology74, 1224, 1978.

    PubMed  CAS  Google Scholar 

  44. Teng C. S. T., Ho P. W. M., Yeung R. T. T.: Down-regulation of insulin receptors in postne-crotic cirrhosis of liver — J. clin. Endocrinol.55, 524, 1982.

    Article  CAS  Google Scholar 

  45. VanThiel D. H., Gavaller J. S., Lester R.: Plasma estrone and prolactin concentration are elevated in men with gynecomastia and spider angioma — Gastroenterology68, 934, 1975.

    Google Scholar 

  46. Wajchenberg B. L., Hoxter G., Mello E. H. L., Ulhoa Cintra A. B.: Nonesterified and esterified fatty acids in hepatocellular disease — Lanceti, 1218, 1960.

    Article  Google Scholar 

  47. Winkler B., Rathgeb I., Steele R., Altszuler N.: Effect of ovine prolactin administration on free fatty acids metabolism in the normal dog — Endocrinology88, 1349, 1971.

    Article  PubMed  CAS  Google Scholar 

  48. Yeung R. T. T., Wang C. C. L.: A study of carbohydrate metabolism in postnecrotic cirrhosis of the liver — Gut15, 907, 1974.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Istituto di Clinica Medica Generale e Terapia Medica, Università di Parma, Parma

    Enzo Bonora, Carlo Coscelli & Ugo Butturini

  2. Istituto di Clinica Medica Generale e Terapia Medica IV, Università di Firenze, Firenze

    Stefano Orioli, Giampiero Buzzelli & Paolo Gentilini

Authors
  1. Enzo Bonora
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  2. Stefano Orioli
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  3. Carlo Coscelli
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  4. Giampiero Buzzelli
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  5. Paolo Gentilini
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  6. Ugo Butturini
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Supported by grants from the Ministry of Public Education and grant No. 83/02132.04 from the National Research Council (C.N.R.), Rome.

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Bonora, E., Orioli, S., Coscelli, C. et al. Possible roles of insulin, glucagon, growth hormone and free fatty acids in the pathogenesis of insulin resistance of subjects with chronic liver diseases. Acta diabet. lat 21, 241–250 (1984). https://doi.org/10.1007/BF02642897

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  • DOI: https://doi.org/10.1007/BF02642897

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