Summary
The portal vein was catheterized via the umbilical vein under local anaesthesia in 10 non-diabetic subjects about to undergo exploratory laparotomy and in 8 patients with liver cirrhosis. Immunoreactive insulin (IRI) and glucagon (IRG) were assayed in portal and peripheral blood before and during IV infusion of glucose (0.33 g/kg) or arginine (25 g). Basal peripheral plasma (IRI) levels were raised in cirrhotic patients (19±2 versus 10±1 μU/ml; P<0.001). Basal portal insulin values, however, did not differ in the two groups. After glucose cirrhotic patients had higher peripheral insulin concentrations, compared to controls, significant at 45 and 60 minutes. In contrast portal insulin levels were higher in controls than in cirrhotics by 1 minute (403±43 versus 158±38 μU/ml; P<0.001) and remained so for the 60 minutes of study. Similarly, after arginine cirrhotics had significantly higher peripheral insulin concentrations and lower portal concentrations than controls. Peak portal vein insulin levels were delayed in cirrhotics (168±16 μU/ml at 3 min) compared with controls (413±25 μU/ml at 1 min). In the basal state both portal and peripheral glucagon levels were higher in cirrhotics than control subjects. Unlike in controls, IV glucose did not suppress glucagon secretion in cirrhotic patients. Peripheral plasma glucagon concentrations after arginine were also consistently higher in cirrhotics than controls, but unlike insulin portal venous glucagon levels were also raised (1800±360 pg/ml, cirrhotics; 960±87 pg/ml, controls; P<0.001; 1 min after arginine infusion). We conclude that insulin secretion is decreased in liver cirrhosis and that the peripheral hyperinsulinaemia observed reflects diminished hormone metabolism. The high plasma glucagon levels observed in cirrhotic patients are the result of pancreatic hypersecretion of glucagon.
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Assan, R.: In vivo metabolism of glucagon. In: Glucagon. Molecular, physiology, clinical and therapeutic implications. Lefebvre, P. J., Unger, R. H. (Eds.), pp. 47–59. Oxford: Pergamon 1972
Berkowitz, D.: Glucose tolerance, free fatty acid, and serum insulin responses in patients with cirrhosis. Am. J. Dig. Dis.14, 691–699 (1969)
Bittner, R., Beger, H. G., Kraas, E.: Oscillation in insulin response to glucose stimulation. Measurements in the portal vein in the postoperative period. Horm. Metab. Res.6, 423–424 (1974)
Blackard, W. G., Rubenstein, A. H.: Proinsulin, insulin and Cpeptide concentrations in human portal and peripheral blood. J. Clin. Invest.55, 1278–1283 (1975)
Cerasi, E., Hallberg, D., Luft, R.: Simultaneous determination of insulin in brachial and portal veins during glucose infusion in normal and prediabetic subjects. Horm. Metab. Res.2, 303–304 (1970)
Collins, J. R., Crofford, O. B.: Glucose intolerance and insulin resistance in patients with liver disease. Arch. Intern. Med.124, 142–148 (1969)
Conard, V.: Mesure de l'assimilation du glucose; bases théoriques et applications cliniques. Acta Gastroenterol. Belg.18, 655–705 (1955)
Creutzfeldt, W., Frerichs, H., Kraft, W.: The intravenous tolbutamide test in liver disease. Acta Diabetol. Lat.4 [Suppl. 1], 209–230 (1967)
Duprey, J., Lubetzki, J., Warnet, A.: Étude de la tolérance au glucose, de l'insuline-sécrétion et de la sensibilité a l'insuline endogène au cours des affections alcooliques du foie. Diabète22, 143–149 (1974)
Efendic, S., Cerasi, E., Luft, R.: Quantitative study on the potentiating effect of arginine on glucose-induced insulin response in healthy, prediabetic, and diabetic subjects. Diabetes23, 161–171 (1974)
Erwald, R., Hed, R., Nygren, A., Rojdmark, S., Sundblad, L., Wiechel, K. L.: Immunoreactive insulin in the portal and the peripheral venous blood after intravenous tolbutamide administration. Diabetes20, 686–690 (1971)
Felber, J. P., Magnenat, P., Vannotti, A.: Tolèrance au glucose diminuée et réponse insulinique élevée dans la cirrhose. Schweiz. Med. Wochenschr.97, 1537–1539 (1967)
Franckson, J. R. M., Ooms, H. A.: The catabolism of insulin in the dog: evidence for two catabolic pathways. Postgrad. Med. J.49, 931–939 (1974)
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, 330–339 (1974)
Herbert, V., Lau, K. S., Gottlieb, C. W., Bleicher, S. J.: Coated charcoal immunoassay of insulin. J. Clin. Endocrinol. Metab.25, 1375–1384 (1965)
Hernandez, A., Zorrilla, E., Gershberg, H.: Decreased insulin production, elevated growth hormone levels and glucose intolerance in liver disease. J. Lab. Clin. Med.73, 25–33 (1969)
Jaspan, J. B., Huen, A. H. J., Morley, C. G., Moosa, A. R., Rubenstein, A. H.: The role of the liver in glucagon metabolism. J. Clin. Invest.60, 421–428 (1977)
Johnston, D. G., Alberti, K. G. M. M., Faber, O. K., Binder, C., Wright, R.: Hyperinsulinism of hepatic cirrhosis: diminished degradation or hypersecretion? Lancet1977 I, 10–12
Johnston, D. G., Alberti, K. G. M. M., Wright, R., Smith-Laing, G., Stewart, A. M., Sherlock, S., Faber, O., Binder, C.: C-peptide and insulin in liver disease. Diabetes27 [Suppl. 1], 201–206 (1978)
Kaden, M., Harding, P., Field, J. B.: Effect of intraduodenal glucose administration on hepatic extraction of insulin in the anesthetized dog. J. Clin. Invest.52, 2016–2028 (1973)
Kakiuchi, S., Tomizawa, H.H.: Properties of a glucagondegrading enzyme of beef liver. J. Biol. Chem.239, 2160–2164 (1964)
Kanazawa, Y., Kukuya, T., Ide, T., Kosaka, K.: Plasma insulin responses to glucose in femoral, hepatic, and pancreatic veins in dogs. Am. J. Physiol.211, 442–448 (1966)
Kaplan, N., Madison, L. L.: Effect of endogenous insulin secretion on the magnitude of hepatic binding of labelled-insulin during a single transhepatic circulation in human subjects. Clin. Res.7, 248 (1959)
Kasperska, T., Lawecki, J., Rogala, H., Czyzyk, A.: The behaviour of insulinaemia in patients with liver cirrhosis after intravenous administration of glucose, tolbutamide and glucagon. Diabetologia7, 391–394 (1971)
Kraas, E., Bittner, R., Meves, M., Beger, H. G.: Insulinkon-zentrationen in Pfortaderblut des Menschen nach Glucose-Infusion. Klin. Wochenschr.52, 404–406 (1976)
Lefebvre, P., Fischer, U., Jutzi, E., Hommel, H., Luyckx, A. S.: Rôle du foie dans la captation du glucagon endogène chez le chien anesthésié. Ann. Endocrinol. (Paris)39, 347–348 (1978)
Lefebvre, P. J., Luyckx, A. S.: Effect of acute kidney exclusion of renal arteries on peripheral plasma glucagon levels and pancreatic glucagon production in the anesthetized dog. Metabolism24, 1169–1183 (1975)
Lund, B., Schmidt, A., Deckert, T.: Portal and cubital serum insulin during oral, portal and cubital glucose tolerance tests. Acta Med. Scand.197, 275–281 (1975)
Madison, L. L., Combes, B., Unger, R. H., Kaplan, N.: The relationship between the mechanism of action of the sulphonylureas and the secretion of insulin into the portal circulation. Ann. N.Y. Acad. Sci.74, 548–556 (1959)
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.289, 1107–1111 (1973)
Megyesi, C., Samols, E., Marks, V.: Glucose tolerance and diabetes in chronic liver disease. Lancet1967 II, 1051–1055
Mondon, C. E., Olefsky, J. M., Dolkas, C. B., Reaven, G. M.: Removal of insulin by perfused rat liver: effect of concentration. Metabolism24, 153–160 (1975)
Mortimer, G. E., Tietze, F., Stetten, D.: Metabolism of insu-lin-I131, studies in isolated, perfused rat liver and hind limb preparations. Diabetes8, 307–314 (1959)
Rayfield, E. J., Faulkner, R. T., Czajkowski, W.: Portal and peripheral vein insulin responses to intravenous glucose in the rhesus monkey. J. Lab. Clin. Med.87, 919–924 (1976)
Record, C. O., Alberti, K. G. M. M., Williamson, D. H., Wright, R.: Glucose tolerance and metabolic changes in human viral hepatitis. Clin. Sci. Mol. Med.45, 677–690 (1973)
Röjdmark, S., Bloom, G., Chou, M. C. Y., Field, J. B.: Hepatic extraction of exogenous insulin and glucagon in the dog. Endocrinology102, 806–813 (1978)
Samaan, N. A., Stone, D. B., Eckhardt, R. D.: Serum glucose, insulin and growth hormone in chronic hepatic cirrhosis. Arch. Intern. Med.124, 149–152 (1969)
Samols, E., Ryder, J. A.: Studied on tissue uptake of insulin in man using differential immunoassay for endogenous and exogenous insulin. J. Clin. Invest.40, 2092–2102 (1961)
Sherwin, R. S., Bastl, C., Finkelstein, F. O., Fisher, M., Black, H., Hendler, R., Felig, P.: Influence of uremia and hemodialysis on the turnover and metabolic effects of glucagon. J. Clin. Invest.57, 722–731 (1976)
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, 1224–1228 (1978)
Sherwin, R., Joshi, P., Hendler, R., Felig, P., Conn, H. O.: Hyperglucagonemia in Laennec's cirrhosis. N. Engl. J. Med.290, 239–242 (1974)
Shurberg, J. L., Resnick, R. H., Koff, R. S., Ross, E., Baum, R. A., Pallotta, J. A.: Serum lipids, insulin and glucagon after portacaval shunt in cirrhosis. Gastroenterology72, 301–304 (1977)
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.41, 682–689 (1962)
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Greco, A.V., Crucitti, F., Ghirlanda, G. et al. Insulin and glucagon concentrations in portal and peripheral veins in patients with hepatic cirrhosis. Diabetologia 17, 23–28 (1979). https://doi.org/10.1007/BF01222973
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DOI: https://doi.org/10.1007/BF01222973