Regulation of urea synthesis by diet protein and carbohydrate in normal man and in patients with cirrhosis: Relationship to glucagon and insulin

Danish Medical Bulletin

Volumn 44, Issue 3, 1997, Pages 225-241

  Hamberg, Ole ^a,b  

^a Rigshospitalet   (Denmark)

^b GLOSTRUP UNIVERSITY HOSPITAL   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCAGON; GLUCOSE; INSULIN; NITROGEN; UREA;

CARBOHYDRATE INTAKE; GLUCAGON BLOOD LEVEL; HUMAN; HYPERGLYCEMIA; LIVER CIRRHOSIS; MALNUTRITION; NITROGEN METABOLISM; PATHOPHYSIOLOGY; PROTEIN INTAKE; REVIEW; UREA CYCLE; URINARY EXCRETION;

DIETARY CARBOHYDRATES; DIETARY PROTEINS; HUMANS; LIVER CIRRHOSIS; UREA;

EID: 0030741823     PISSN: 09078916     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (219)

1. Abumrad NN, Rabin D, Wise KL, Lacy WW. The disposal of an intravenously administered amino acid load across the human forearm. Metabolism 1982; 31: 463-470.
2. Adibi SA, Morse EL, Amin PA. Role of insulin and glucose in the reduction of hypoaminoacidemia in man: studies in normal, juvenile diabetic, and insuloma patients. J Lab Clin Med 1975; 86: 395-409.
3. Ahmed M, Nuttall FQ, Gannon MC, Lamusga RF. Plasma glucagon and α-amino nitrogen response to various diets in normal humans. Am J Clin Nutr 1980; 3: 1917-1924.
4. Aikawa T, Matsutaka H, Takezawa K, Ishikawa E. Gluconeogenesis and amino acid metabolism. Biochim Biophys Acta 1972; 279: 234-244.
5. Alberti KGMM, Christensen SE, Iversen J, Sayer-Hansen K, Christensen NJ, Hansen AP, Lundbaek K, Ørskov H. Inhibition of insulin secretion by somatostatin. Lancet 1973; ii: 1299-1301.
6. Almdal TP, Vilstrup H. Effects of streptozotocin-induced diabetes and diet on nitrogen loss from organs and the capacity of urea synthesis in rats. Diabetologia 1987; 30: 952-956.
7. Almdal TP, Vilstrup H. Exogenous hyperglucagonaemia in insulin controlled diabetic rats increases urea excretion and nitrogen loss from organs. Diabetologia 1988; 31: 836-841.
8. Almdal TP, Jensen T, Vilstrup H. Increased hepatic efficacy of urea synthesis from alanine in insulin-dependent diabetes mellitus. Eur J Clin Invest 1990; 20: 29-34 (A).
9. Almdal TP, Heindorff H, Bartram L, Vilstrup H. Increased amino acid clearance and urea synthesis in a patient with glucagonoma. GUT 1990; 31: 946-948 (B).
10. Almdal TP. Importance of glucagon for nitrogen loss in diabetes. Dan Med Bull 1991; 38: 113-120.
11. Almdal TP, Heindorff H, Hamberg O, Vilstrup H. Glucagon increases hepatic urea synthesis irrespective of insulin concentration. Hepato-gastroenterology 1993; 40: 3 (Abstract)(A).
12. Almdal T, Heindorff H, Hansen BA, Vilstrup H. Xylitol normalizes the accelerated hepatic capacity for conversion of amino nitrogen to urea nitrogen in diabetic rats. JPEN 1993; 17: 345-347 (B).
13. Andreasen PB, Ranek L, Statland BE Tygstrup N. Clearance of antipyrine -dependence of quantitative liver function. Eur J Clin Invest 1974; 4: 129-134.
14. Aoki TT, Müller WA, Brennan MF, Cahill GF. Metabolic effects of glucose in brief and prolonged fasted man. Am J Clin Nutr 1975; 28: 507-511.
15. 13C] leucine. Clin Sci 1989; 76: 447-454.
16. Bhathena SJ, Voyles NR, Smith S, Recant L. Decreased glucagon receptors in diabetic rat hepatocytes. J Clin Invest 1978; 61: 1488-1497.
17. Bianchi G, Marchesini G, Vilstrup H, Fabbri A, De Mitri MS, Zoli M, Pisi E. Hepatic amino-nitrogen clearance to urea-nitrogen in control subjects and in patients with cirrhosis: A simplified method. Hepatology 1991; 13: 460-466.
18. Blackard WG, Nelson NC. Portal and peripheral vein immunoreactive insulin concentrations before and after glucose infusion. Diabetes 1970; 19: 302-306.
19. Blackard WG, Nelson NC, Andrews SS. Portal and peripheral vein immunoreactive glucagon concentrations after arginine or glucose infusions. Diabetes 1974; 23: 199-202.
20. Boden G, Master RW, Rezvani I, Palmer JP, Lobe TE, Owen OE. Glucagon deficiency and hyperaminoacidemia after total pancreatectomy. J Clin Invest 1980; 65: 706-716.
21. Boden G, Rezvani I, Owen OE. Effects of glucagon on plasma amino acids. J Clin Invest 1984; 73: 785-793..
22. Boden G, Tappy L, Jadali F, Hoeldtke RD, Rezvani I, Owen O. Role of glucagon in disposal of an amino acid load. Am J Physiol 1990; 259: E225-E232.
23. Brennan MF, Fitzpatrick GF, Cohen KH, Moore FD. Glycerol: Major contributor to the short term protein sparing effect of fat emulsion in normal man. Ann Surg 1974; 182: 386-394.
24. Brodan V, Brodanova M, Andel M, Kuhn E. The effect of glucagon on free plasma amino acids in cirrhosis and healthy controls. Acta hepato-gastroenterol 1978; 25: 23-29.
25. Cahill GF. Physiology of insulin in man. Diabetes 1971; 29: 785.
26. Castellino P, Luzi L, Simonson DC, Haymond M, DeFronzo RA. Effect of insulin and plasma amino acid concentrations on leucine metabolism in man. J Clin Invest 1987; 80: 1784-1793..
27. Cathcart EP. The influence of carbohydrates and fats on protein metabolism. J Physiol 1909; 39: 311-330.
28. Cherrington AD, Stevenson RW, Steiner KE, Myers SR, Adkins BA, Abumrad NN, Williams PE. Insulin, glucagon, and glucose as regulators of hepatic glucose uptake and production in vivo. Diab Metab Rev 1987; 3: 307-332.
29. Chiasson JL, Atkinson RL, Cherrington AD, Keller U, Sinclair-Smith BC, Lacy WW, Liljenquist JE. Effects of insulin at two dose levels on gluconeogenesis from alanine in fasting man. Metabolism 1980; 29: 810-818.
30. Chikenji T, Elwyn DH, Gil KM, Danforth E, Askanazi J, Kinney JM. Effects of increasing glucose intake on nitrogen balance and energy expenditure in malnourished adult patients receiving parenteral nutrition. Clin Sci 1987; 72: 489-501.
31. Clowes GHA, Heideman M, Lindberg B, Randall HT, Hirsch EF, Cha C-J, Martin H. Effects of parental alimentation on amino acid metabolism in septic patients. Surgery 1980; 88: 531-543.
32. Crofford OB, Felts BW, Lacy WW. Effect of glucose infusion on the individual plasma free amino acids in man. Proc Soc Exp Biol Med 1964; 117: 11-14.
33. Daniel PM, Pratt OE, Spargo E. The mechanism by which glucagon induces the release of amino acids from muscle and its relavance to fasting. Proc R Soc Lond B 1977; 196: 347-365.
34. Davis SN, Dobbins R, Tarumi C, Colbum C, Neal D, Cherrington AD. Effects of different insulin levels on response to equivalent hypoglycemia in conscious dogs. Am J Physiol 1992; 263: E688-E695.
35. DeFronzo RA, Ferrannini E, Hendler R, Felig P, Wahren J. Regulation of splanchnic and peripheral glucose uptake by insulin and hyperglycemia in man. Diabetes 1983; 32: 35-45.
36. Dudley FJ, Alford FP, Chisholm DJ, Findlay. Effect of portasystemic venous shunt surgery on hyperglucagonaemia in cirrhosis: paired studies of preand post-shunted subjects. Gut 1979; 20: 817-824.
37. Døssing M, Poulsen HE, Andreasen PB, Tygstrup N. A simple method for the determination of antipyrine clearance. Clin Pharmacol Ther 1982; 32: 392-396.
38. Elia M, Ilic V, Bacon S WIlliamson DH, Smith R. Relationship between the basal blood alanine concentration and the removal of an alanine load in various clinical states in man. Clin Sci 1980; 58: 301-309.
39. Elwyn DH, Parikh HC, Shoemaker WC. Amino acid movements between gut, liver, and periphery in unanesthetized dogs. Am J Physiol 1968; 215(5): 1260-1275.
40. Eriksson LS, Law DH, Sato Y, Wahren J. Influence of somatostatin on splanchnic haemodynamics in patients with cirrhosis. Clin Physiol 1984; 4: 5-11.
41. Fabbri A, Bianchi GP, Bugianesi E, Zoli M, Marchesini G. Total body water (TBW) and one-sample antipyrine clearance (AP Cl) in advanced liver cirrhosis. J Hepatol 1991; 13(suppl 2): S26 (Abstract).
42. Fabbri A, Marchesini G, Bianchi GP, Bugianesi E, Bortoluzzi L, Zoli M, Pisi E. Unresponsiveness of hepatic nitrogen metabolism to glucagon infusion in patients with cirrhosis: Dependence on liver cell failure. Hepatology 1993; 18: 28-35.
43. Fawcett JK, Scott JE. A rapid and precise method for the determination of urea. J Clin Path 1960; 13: 156-159.
44. Fehlmann M, Le Cam A, Freychet P. Insulin and glucagon stimulation of amino acid transport in isolated rat hepatocytes. J Biol Chem 1979; 254-10431-10435.
45. Felig P, Wahren J. Influence of endogenous insulin secretion on splanchnic glucose and amino acid metabolism in man. J Clin Invest 1971; 50: 1702-1711.
46. Felig P. The glucose-alanine cycle. Metabolism 1973; 22: 179-207.
47. Felig P, Gusberg R, Hendler R, Gump FE, Kinney JM. Concentrations of glucagon and the insulin: glucagon ratio in the portal and peripheral circulation. Proc Soc Exp Biol Med 1974; 147: 88-90.
48. Felig P. Influence of oral glucose ingestion on splanchnic glucose and gluconeogenic subtrate metabolism in man. Diabetes 1975; 24: 468-75.
49. Ferrannini E, DeFronzo RA, Gusberg R, Tepler J, Jacob R, Aaron M, Smith D, Barrett E. Splanchnic amino acid and glucose metabolism during amino acid infusion in dogs. Diabetes 1988; 37: 237-245.
50. Ferenci P, Bratusch-Marrain P, Waldhausl WK, Nowotny P, Korn A. Impaired plasma amino-acid clearance in patients with cirrhosis of the liver and portocaval shunt: its relation to insulin resistance. Eur J Clin Invest 1984; 14: 255-261.
51. Fischer JE, Yoshimura N, Aguirre, James JH, Cummings MG, Abel RM, Deindoerfer F. Plasma amino acids in patients with hepatic encephalopathy. Am J Surg 1974; 127: 40-47.
52. Fitzpatrick GF, Meguid MM, O'Connell RC, O'Connor NE, Ball MR, Brennan MF. Nitrogen sparing by carbohydrate in man: Intermittent or continuous enterai compared with continuous parenteral glucose. Surgery 1975; 78: 105-113.
53. Floyd JC, Fajans SS, Pek S, Thiffault CA, Knopf RF, Conn JW. Synergistic effect of essential amino acids and glucose upon insulin secretion in man. Diabetes 1970; 19: 102-108.
54. Folin O. Laws govering the chemical composition of urine. Am J Physiol 1905; 13: 66-115.
55. Francavilla A, Jones AF, Starzl TE. Cyclic AMP metabolism and adenylate cyclase concentration in patients with advanced hepatic cirrhosis. Gastroenterology 1978; 75: 1026-1032.
56. Fraser CCL, Adrieff A. Hepatic encephalopathy. N Engl J Med 1985; 313: 865-873.
57. Fukagawa NK, Minaker KL, Young VR, Rowe JW. Insulin dose-dependent reductions in plasma amino acids in man. Am J Physiol 1986; 250: E13-E17.
58. Gamble JL. Physiological information gained from studies on life raft ration. Harvey Lect 1947; 42: 247-273.
59. Gelfand RA, Barett EJ. Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man. J Clin Invest 1987; 80: 1-6.
60. Georgieff M, Moldawer LL, Bistrian BR, Blackburn GL. Xylitol. An energy source for intravenous nutrition after trauma. JPEN 1985; 9: 199-209.
61. Georgieff M, Pscheidl E, Moldawer LL, Bistrain BR, Blackburn GL. Mechanisms of protein conservation during xylitol infusion after burn injuri in rats: isotope kinetics and indirect calorimetry. Eur J Clin Invest 1991; 21: 249-258.
62. Gibson JA, Park NJ, Sladen GE, Dawson AM. The role of the colon in urea metabolism in man. Clin Sci Mol Med 1976; 50: 51-59.
63. Goodwin JF. Spectrophotometric quantitation of plasma and urinary amino nitrogen with fluorodinitrobenzene. Stand Meth Clin Chem 1970; 6: 89-98.
64. Greco AV, Crucitti F, Ghirlanda G, Manna R, Altomonte L, Rebruzzi AG, Bertoli A. Insulin and glucagon concentrations in portal and peripheral veins on patients with hepatic cirrhosis. Diabetologia 1979; 17: 23-28.
65. Greco AV, Altomonte L, Ghirlanda G, Rebuzzi AG, Manna R, Bertoli A. Somatostatin infusion in liver cirrhosis: Glucagon control of glucose homeostasis. Diabetologia 1980; 18: 187-191.
66. Greenberg GR, Marliss EB, Anderson GH, Langer B, Spence W, Tovee EB, Jeejeebhoy KN. Protein-sparing therapy in postoperative patients. N Engl J Med 1976; 294: 1411-1416.
67. Hamberg O, Rumessen JJ, Gudmand-Høyer E. Blood glucose response to pea fiber: comparisons with sugar beet fiber and wheat bran. Am J Clin Nutr 1989; 50: 324-328.
68. Hamberg O, Ovesen L, A Dorfeldt, S Loft, J Sonne. The effect of dietary energy end protein deficiency on drug metabolism. Studies with oxazepam, antipyrine and metronidazole. Eur J Clin Pharmacol 1990; 38: 567-570.
69. Hamberg O, Nielsen K, Vilstrup H. Effects of an increase in protein intake on hepatic efficacy for urea synthesis in healthy subjects and in patients with cirrhosis of the liver. J Hepatol 1992: 14: 237-244.
70. Hamberg O, Vilstrup H. Importance of hyperglycaemia for suppression of urea synthesis by glucose in man. Surg Res Comm 1993; 14: 41-49 (A).
71. Hamberg O, Vilstrup H. Liver and Skeletal muscles. Muscle wasting in cirrhosis. Extrahepatic manifistations of liver disease. Kluwer academic publisher. Ed. R. Schmid, L. Bianchi, W. Gerok, K.P. Maier, 1993, 164-170 (B).
72. Hamberg O, Vilstrup H. Regulation of urea synthesis by glucose: Relation to glucagon. Clin Nutr 1994; 13: 183-191 (A).
73. Hamberg O, Vilstrup H. Effects of insulin and glucose on urea synthesis in normal man, independent of pancreatic hormone secretion. J Hepatol 1994; 21: 381-387 (B).
74. Hamberg O, Vilstrup H. Effects of glucose on hepatic conversion of aminonitrogen to urea in patients with cirrhosis: Relationship to glucagon. Hepatology 1994; 19: 45-54 (C).
75. Hamberg O, Vilstrup H. A rapid method for the determination of hepatic amino nitrogen to urea nitrogen conversion. The Functional Hepatic Nitrogen Clearance. Scand J Clin Lab Invest 1994; 54: 377-383 (D).
76. Hamberg O, Almdal TP. Effects of xylitol on urea synthesis in normal man: Relation to glucagon JPEN 1996; 20: 139-144.
77. Hansen BA, Vilstrup H. Increased intestinal hydrolysis of urea in patients with alcoholic cirrhosis. Scand J Gastroenterol 1985; 20: 346-350.
78. Hansen BA, Krog B, Vilstrup H. Insulin and glucose decreases the capacity of urea-N synthesis in the rat. Scand J Clin Lab Invest 1986; 5: 213-216.
79. Hansen BA, Almdal T, Vilstrup H. The effect of xylitol versus glucose on the capacity of urea-N synthesis and alanine metabolism in the rat. Clin Nutr 1989; 8: 109-112.
80. Hattori N, Kurahahci H, Ikekubo K, Ishihara T, Moridera K, Hino M, Saiki Y, Imura H. Serum growth hormone-binding protein, insulin-like growth factor-I. and growth hormone in patients with liver cirrhosis. Metabolism 1992; 41; 377-381.
81. Heding L. Radioimmunological determination of pancreatic and gut glucagon in plasma. Diabetologia 1971; 7: 10-18.
82. Heding L. Determination of insulin (IRI) in insulin treated diabetic patients. Diabetologia 1972; 8: 260-268.
83. Heindorff H. Vilstrup H, Bucher D, Billesbølle P, Thygesen V. Increased hepatic amino nitrogen conversion after elective cholecystectomy in man. Clin Sci 1988; 74: 539-545.
84. Heindorff H, Vilstrup H, Almdal T, Harvald T, Nielsen J, Dalsgaard S. Elective cholecystectomy increases plasma amino-acid clearance and hepatic capacity for urea synthesis for one week. Clin Nutr 1991; 10: 10-17.
85. Heindorff H. The hepatic catabolic stress response. Hormonal regulation of urea synthesis after surgery. Dan Med Bull 1993; 40: 224-234.
86. Herrera MG, Kamm D, Ruderman N, Cahill GF. Non-hormonal factors in the control of gluconeogenesis. Adv. Enzyme Regul. 1966; 4: 225-235.
87. Hoogwerf BJ, Laine DC, Greene E. Urine C-peptide and creatinine (Jaffe method) excretion in healthy young adults on varied diets: sustained effects of varied carbohydrtae, protein, and meat content. Am J Clin Nutr 1986; 43: 350-360.
88. Hoppe F. Ueber den Einfluss des Rohrzuckers auf die Verdauung und Ernarung. Arch Path Anat u Physiol 1856; 10: 144.
89. Jahoor F, Wolfe RR. Regulation of urea production by glucose in vivo. Am J Physiol 1987; 253: E543-E550.
90. Jefferson JS, Schworer CM, Tolman ET. Growth hormone stimulation of amino acid transport and utilization by perfused rat liver J Biol Chein 1975; 250: 197-204.
91. Jelinek JL, Lok S, Rosenberg GB, Smith RA, Grant FJ, Biggs S, Bensch PA, Kuijper JL, Sheppard PO, Sprecher CA, O'Hara PJ, Foster D, Walker KM, Chen LHJ, McKernan PA, Kindsvogel W. Expression cloning and signaling properties of the rat glucagon receptor. Science 1993; 259: 1614-1616.
92. Johnston DG, Davies, Prescott RWG. Regulation of growth hormone secretion in man: a review. J Roy Soc Med 1985; 78: 319-327.
93. Jones EA, Smallwood RA, Cragie A, Rosenoer VM. The enterohepatic circulation of urea nitrogen. Clin Sci 1969; 37: 825-836.
94. Kadabi UM, Eisenstein AB, Tucci J, Pellicone J. Hyperglucagonemia in hepatic cirrhosis: Its relation to hepatocellular dysfunction and normalization on recovery. Am J Gastroenterol 1984; 79: 143-149.
95. Kadabi UM, Eisenstein AB, Konda J. Elevated plasma ammonia level in hepatic cirrhosis: Role of glucagon. Gastroenterology 1985; 88: 750-756.
96. Kadabi UM. Hepatic regulation of pancreatic α-cell function. Metabolism 1993; 42: 535-543.
97. Kearns PJ, Young H, Garcia G, Blaschke T, O'Hanlon G, Rinki M, Sucher K, Gregory P. Accelerated improvement of alcoholic liver disease with enteral nutrition. Gastroenterology 1992; 102: 200-205.
98. Keller U, Sonnenberg GE, Burckhardt D, Perruchoud A. Evidence for an augmented glucagon dependence of hepatic glucose production in cirrhosis of the liver. J Clin Endocrinol Metab 1982; 54: 961-968.
99. Khatra BS, Smith RB, Millikan WJ, Sewell CW, Warren D, Rudman D. Activities of Krebs-Henseleit enzymes in normal and cirrhotic human liver. J Lab Clin Med 1974; 84: 708-715.
100. Kirk E. Amino acid and ammonia metabolism in liver disease. Dissertation. Levin & Munksgaard Publishers, Copenhagen, Denmark, 1936: 80-89.
101. Kitagawa Y, Ryall J, Nguyen M, Shore GC. Expression of carbamoyl-phosphate synthetase I mRNA in Reuber hepatoma H-35 cells. Regulation by glucocorticoid and insulin. Biochim Biophys Acta 1985; 825: 148-153.
102. Koecker DJ, Ruch W, Chideckel E, Palmer J, Goodner CJ, Ensinck J, Gale CC. Somatostatin: Hypothalamic inhibitor of the endocrine pancreas. Science 1974; 184: 482-484.
103. Krebs HA, Hems R, Lund P. Some regulatory mechanisms in the synthesis of urea in the mammalian liver. Adv Enzyme Regul 1973; 11: 361-377.
104. Kruszynska YT, Williams N, Perry M, Home P. The relationship between insulin sensitivity and skeletal muscle enzyme activities in hepatic cirrhosis. Hepatology 1988; 8: 1615-1619.
105. Kruszynska YT, Meyer-Alber A, Darakhshan F, Home PD, McIntyre N. Metabolic handling of orally administered glucose in cirrhosis. J Clin Invest 1993; 91: 1057-1066.
106. Kugler B, Schricker T, Trager K, Schutz W, Georgieff M. Effects of glucose and xylitol on protein-and carbohydrate metabolism after trauma and in sepsis. Clin Nutr 1992; 11(suppl): 43 (Abstract).
107. Lin RC, Snodgrass PJ, Rabier D. Induction of urea cycle enzymes by glucagon and dexamethason in monolayer culture of adult rat hepatocytes. J Biol Chem 1982; 237: 5061-5067.
108. Long CL, Jeevanandam M, Kinney JM. Metabolism and recycling of urea in man. Am J Clin Nutr 1978; 31: 1367-1382.
109. Long CL, Kinney JM, Geiger JW. Nonsuppressability of gluconeogenesis by glucose in septic patients. Metabolism 1976; 25 193-201.
110. Mackrell DJ, Sokal JE. Antagonism between the effects of insulin and glucagon on the isolated liver. Diabetes 1969; 18: 724-732.
111. Maier KP, Talke H, Gerok W. Activities of urea-cycle enzymes in chronic liver disease. Klin Wochenschr. 1979; 57: 661-667.
112. Maier KP. Progress in the treament of portal-systemic encephalopathy (PSE). J Hepatol 1987; 5: 355-361.
113. Marchesini G, Forlani G, Zoli M, Angioloni A, Scolari MP, Bianchi FB, Pisi E. Insulin and glucagon levels in liver cirrhosis. Relationship with plasma amino acid imbalance of chronic hepatic encephalopathy. Dig Dis Sci 1979; 24: 594-601 (A).
114. 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. Diab Met 1979; 5: 135-139 (B).
115. Marchesini G, Bianchi GP, Zoli M, Dondi C, Forlani G, Melli A, Bua V, Vannini P, Pisi E. Plasma amino acid response to protein ingestion in patients with liver cirrhosis. Gastroenterology 1983; 85: 283-90.
116. Marchesini G, Bianchi GP, Vilstrup H, Checchia GA, Patrono D, Zoli M. Plasma clearances of branched-chain amino acids in control subjects and in patients with cirrhosis. J Hepatol 1987; 4: 108-117.
117. Marchuk JB, Finley RJ, Groves AC, Wolfe LI, Holliday RL, Duff JH. Catabolic hormones and substrate patterns in septic patients. J Surg Res 1977; 23: 177.
118. Marco J, Diego J, Villanueva ML, Diaz-Fierros M, Valverde I, Segovia JM. Elevated plasma glucagon levels in cirrhosis of the liver. N Engl J Med 1973; 289: 1107-1111.
119. McCullough AJ, Mullen KD, Kalhan SC. Body cell mass and leucine metabolism in cirrhosis. Gastroenterology 1992; 102: 1325-1333.
120. Meijer AJ, Lamers WH, Chamuleau RAFM. Nitrogen metabolism and ornithine cycle function. Physiol Rew 1990; 70: 701-748.
121. Mendenhall C, Bongiovanni G, Goldberg S et al. VA Cooperative study on alcoholic hepatitis III: Changes in protein-calorie malnutrition associated with 30 days of hospitalization with and without enterai nutritional therapy. JPEN 1985; 9: 590-596..
122. Merkel C, Gatta A, Zuin R, Finucci GF, Nosadini R, Ruol A. Effect of somatostatin on splanchnic hemodynamics in patients with liver cirrhosis and portal hypertension. Digestion 1985; 32: 92-98.
123. Metz R, Salter JM, Brunet G. Effect of pyruvate and other substrates on urea synthesis in rat liver slices. Metabolism 1968; 17: 158-167.
124. Miller LL, Burke WT, Haft DE. Interrelations in amino acid and carbohydrate metabolism. Studies of the nitrogen sparing action of carbohydrate with the isolated perfusef rat liver. Fed Proc 1955; 14: 707-716.
125. Miller LL. Glucagon: a protein catabolic hormone in the isolated perfused rat liver. Nature 1960; 185: 248.
126. Millikan WJ, Jr., Henderson JM, Galloway JR, Warren WD, Matthews DE, McGhee A, Kutner MH. In vivo measurement of leucine metabolism with stable isotopes in normal subjects and in those with cirrhosis fed conventional and branched-chain amino acid-enriched diets. Surgery 1985; 98: 405-412.
127. Millward DJ. The hormonal control of protein turnover. Clin Nutr 1990; 9: 155-126.
128. Mirsky A, Heiman JD, Swadesh S. Nitrogen-sparing action of glucose in normal, phlorhizinized and depancreatized dogs. Am J Physiol 1937; 114: 681-688..
129. Mirsky A. The influence of insulin in the protein metabolism of nephrectomized dogs. Am J Physiol 1938; 124: 569-575.
130. Moldawer LL, O'Keefe SJD, Bothe A, Bistrain BR, Blackburn GL. In vivo demonstration of nitrogen-sparing mechanisms for glucose and amino acids in the injured rat. Metab Clin Exp 1980; 29: 173-180.
131. Mondon CE, Mortimore GE. Effects of insulin on amino acid release and urea formation in perfused rat liver. Am J Physiol 1967; 212: 173-178.
132. Morgan MY. Enterai nutrition in chronic liver disease. Acta Chirurgica Scand 1981; 507 (suppl): 81-90.
133. Morita T, Mori M, Tatibana M. Regulation of N-acetyl-L-glutamate degradation in mammalian liver. J Biochem 1982; 91: 563-569.
134. Morris SM, Moncman CL, O' Brien WE. Modulation of mRNA levels for urea cycle enzymes in rat liver by diet and hormones. Ann NY Ac Sci 1986; 478: 292-294.
135. Morrison WL, Bouchier IAD, Gibson JNA, Rennie MJ. Skeletal muscle and whole-body protein turnover in cirrhosis. Clin Sci 1990; 78: 613-619.
136. Mortimore GE. Effect of insulin on release of glucose and urea by isolated rat liver. Am J Physiol 1962; 204: 699-704.
137. Motil KJ, Matthews DE, Bier D, Burke JF, Munro HN, Young VR. Wholebody leucine and lysine metabolism: response to dietary protein intake in young men. Am J Physiol 1981; 240: E712-E721.
138. Mullen KD, Denne SC, McCullough, AJ, Savin SM, Bruno D, Tavil AS, Kalhan SC. Leucine Metabolism in stable cirrhosis. Hepatology 1986; 6: 622-630.
139. Munro HN. Carbohydrate and fat as factors in protein utilization and metabolism. Physiol Rev 1951; 31: 449-488.
140. Müller WA, Faloona GR, Inger RH: The effect of alanine on glucagon secretion. J Clin Invest 1971; 50: 2215-2218.
141. Müting D, Paquet KJ, Koussouris P, Wuzel H. Plasma ammonia and urea-N synthesis rate in human liver cirrhotics. In: Advances in ammonia metabolism and hepatic encephalopathy. Eds Soeters, Wilson, Meijer, Holm. Elsevier. Amsterdam 1988: 91-98.
142. Myers JD. The hepatic blood flow and splanchnic oxygen consumption of man - their estimation from urea production or bromsulphalein excretion during catheterization of the hepatic veins. J Clin Invest 1947; 26: 1130-1137.
143. Myers SR, Biggers DW, Neal DW, Cherrington AD. Intraportal glucose delivery enhances the effects of hepatic glucose load on net hepatic glucose uptake in vivo. J Clin Invest 1991; 88: 158-167.
144. Møller E, McIntosh JF, Van Slyke DD. Studies of urea excretion. II. Relationship between urine volume and the rate of urea excretion by normal adults. J Clin Invest 1928; 6: 427-504.
145. Nair KS, Halliday D, Matthewes DE, Welle SL. Hyperglucagonemia during insulin deficiency accelerates protein catabolism. Am J Physiol 1987; 253: E208-E213.
146. Nielsen K, Kondrup J, Martinsen L, Stilling B, Wikman B. Nutritional assessment and adequacy of dietary intake in hospitalized patients with alcoholic liver cirrhosis. Br J Nutr 1993; 69: 665-679.
147. Nielsen K, Kondrup J, Martinsen L, Døssing H, Larsson B, Stilling B, Jensen MG. Long-term oral refeeding of patients with cirrhosis of the liver. Br J Nutr 1995; 74: 557-567.
148. O'Connell RC, Morgan AP, Aoki TT, Ball MR, Moore FD. Nitrogen conservation in starvation: Gradede response to intravenous glucose. J Clin Endocrinol Metab 1974; 39: 555-563..
149. Owen OE, Reichle FA, Mozzoli MA, Kreulen T, Patel MS, Elfenbein IB, Golsorkhi M, Chang KHY, Rao NS, Sue HS, Boden G. Hepatic, gut, and renal substrate flux rates in patients with hepatic cirrhosis. J Clin Invest 1981; 68: 240-252.
150. Owen OE, Trapp VE, Reichard GA, Mozzoli MA, Moctezuma J. Paul P, Skutches CL, Boden G. Nature of quantity of fuels consumed in patients with alcoholic cirrhosis. J Clin Invest 1983; 72: 1821-1832.
151. Pacitti AJ, Inoue Y, Plumley DA, Copeland EM, Souba WW. Growth hormone regulates amino acid transport in human and rat liver. Ann Surg 1992; 216: 353-362.
152. Pagliassotti MJ, Moore MC, Neal DW, Cherrington AD. Insulin is required for the liver to respond to intraportal glucose delivery in the conscious dog. Diabetes 1992; 41: 1247-1256.
153. Painter EE. Total body water in the dog. Am J Physiol 1940; 129: 744-755.
154. Petersen KF, Hansen BA, Vilstrup H. Time dependent stimulating effect of glucagon on the capacity of urea-N synthesis in rats. Horm Metabol Res 1987; 19: 53-56.
155. Petersen KF, Vilstrup H, Tygstrup N. Effect of dietary protein on the capacity of urea synthesis in rats. Horm Metabol Res 1990; 22: 612-615.
156. Petrides AS, DeFronzo RA. Glucose metabolism in cirrhosis: A review with some perspectives for the future. Diab Met Rew 1989; 5: 691-709.
157. Petrides AS, Luzi L, Reuben A, Reily C, DeFronzo RA. Effect of insulin and plasma amino acid concentration on leucine metabolism in cirrhosis. Hepatology 1991; 14: 432-441 (A).
158. Petrides AS, Groop LC, Riely CA, DeFronzo RA. Effect of physiologic hyperinsulinemia on glucose and lipid metabolism in cirrhosis. J Clin Invest 1991; 88: 561-570 (B).
159. Pietro AS, Rittenberg D. A study of the rate of protein synthesis in humans. Measurements of the urea pool and space. J Biol Chem 1953; 201: 445-455.
160. Pozefsky T, Felig P, Tobin JD, Soeldner JS, Cahill GF. Amino acid balance across tissues of the forearm in portabsorptive man. Effects of insulin at two dose levels. J Clin Invest 1969; 48: 2273-2282.
161. Pozefsky T, Tancredi RG, Moxley RT, Dupre J, Tobin JD. Metabolism of forearm tissues in man. Studies with glucagon. Diabetes 1976; 25: 128-135.
162. Preedy VR, Garlick PJ. The effect of glucagon administration on protein synthesis in skeletal muscles, heart and liver in vivo. J Biochem 1985; 228: 575-581.
163. Price GM, Halliday D, Pacy PJ, Quevedo MR, Millward JD. Nitrogen homeostasis in man: influence of protein intake on the amplitude of diurnal cycling of body nitrogen. Clin Sci 1994; 86: 91-102.
164. Rafoth RJ, Onstad GR. Urea Synthesis after oral protein ingestion in man. J Clin Invest 1975; 56: 1170-1174.
165. Rennie MJ, Edwards HT, Halliday D, Matthews DE, Wolman SL, Millward J. Muscle protein synthesis measured by stable isotope techniques in man: the effects of feeding and fasting. Clin Sci 1982; 63: 519-23.
166. Rocha DM, Faloona GR, Linger RH. Glucagon-stimulating activity of 20 amino acids in dogs. J Clin Invest 1972; 51: 2346-2350.
167. Rogers RQ, Morris JG, Freedland RA. Lack of hepatic enzymatic adaptation to low and high levels of dietary protein in adult cat. Enzyme 1977; 22: 348-356.
168. Royle GT, Molnar JA Wolfe MH, Wolfe RR, Burke JF. Urea, glucose and alanine kinetics in man: effects of glucose infusion. Clin Sci 1982; 62: 553-556.
169. Rypins EB, Henderson JM, Fulenwider JT, Moffitt S, Galambos JT, Warren WD, Rudman D. A tracer method for measuring rate of urea synthesis in normal and cirrhotic subjects. Gastroenterology 1980; 78: 1419-1424.
170. Schimke RT. Adaptive characteristics of urea cycle enzymes in the rat. J Biol Chem 1962; 237: 459-468.
171. Sestoft L, Gammeltoft A. The effect of intraveous xylitol on the concentration of adenine nucleotides in humam liver. Biochem Pharmacol 1976; 25: 2619-2621.
172. Sestoft L. An evaluation of biochemical aspect of intraveous fructose, sorbitol, and xylitol administration in man. Acta Anaesthesiol Scand 1985; 29: 19-29.
173. Shaw JHF, Klein S, Wolfe RR. Assessment of alanine, urea, and glucose interrelationship in normal subjects and in patients with sepsis with stable isotopic tracers. Surgery 1985; 97: 557-567..
174. Shaw JHF, Wolfe RR. An integrated analysis of glucose, fat, and protein metabolism in severely traumatized patients. Ann Surg 1989; 209: 63-72.
175. Sherwin RS, Fisher M, Bessoff J, Snyder N, Hendler R, Conn HO, Felig P. Hyperglucagonemia in cirrhosis: altered secretion and sensitivity to glucagon. Gastroenterology 1978; 74: 1224-1228.
176. Shmueli E, Walker M, Alberti G, Record CO. Normal splanchnic but impaired peripheral insulin-mediated glucose uptake in cirrhosis. Hepatology 1993; 18: 86-95 (A).
177. Shmueli E, Ørskov H, Alberti KGMM, Record CO. Octreotide treament does not improve impaired glucose uptake in cirrhosis. Horm Metab Res 1993; 25: 317-320 (B).
178. Shuck JM, Eaton RP, Shuck LW et al. Dynamics of insulin and glucagon secretions in severely burns patients. J Trauma 1977; 17: 706.
179. Shulman GI, Lacy WW, Liljenquist JE, Keller U, Williams PE, Cherrington AD. Effect of glucose, independent of changes in insulin and glucagon secretion, on alanine metabolism in the conscious dog. J Clin Invest 1980; 65: 496-505.
180. Siess EA, Brocks DG, Lattke HK, Wieland OH. Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate. Biochem J 1977; 166: 225-235.
181. Sigsgård I Almdal TP, Hansen BA, Vilstrup H. Dexamethazone increases the capacity of urea synthesis time dependently and reduces body weight of rats. Liver 1988; 8: 193-197.
182. Sim AJW, Wolfe BM, Young VR, Clarke D, Moore FD. Glucose promotes whole-body protein synthesis from infused aminoacids in man. Lancet 1979; i: 68-71.
183. Smith J, Horowitz J, Henderson JM, Heymsfield S. Enterai hyperalimentation in undernourished patients with cirrhosis and ascites. Am J Clin Nutr 1982; 35: 56-72.
184. Smith-Laing G, Ørskov H, Gore MBR, Sherlock S. Hyperglucagonaemia in cirrhosis. Diabetologia 1980; 19: 103-108.
185. Snodgrass PJ, Lin RC, Müller WA, Aoki TT. Induction of urea cycle enzymes of rat liver by glucagon. J Biol Chem 1978; 253: 2748-2753.
186. Soberman R Brodie BB, Levy BB, Axelrod J Hollander V, Steele M. The use of antipyrine in the measurement of total body water in man. J Biol Chem 1949; 170: 31-42.
187. Sonnenberg GE, Keller U, Perruchoud A, Burckhardt, Gyr K. Effect of somatostatin on splanchnic hemodynamics in patients with cirrhosis of the liver and in normal subjects. Gastroenterology 1981; 80: 526-32.
188. Steiner KE, Mouton SM, Bowles CR, Williams PE, Cherrington AD. The relative importance of first-and second-phase insulin secretion in countering the action of glucagon on glucose turnover in the conscious dog. Diabetes 1982; 31: 964-972.
189. Stephen JML, Waterlow JC. Effect of malnutrition on activity of two enzymes concerned with aminoacid metabolism in human liver. Lancet 1968; i: 118-119.
190. Swart GR, van den Berg JWO, Wattimena JLD, Rietveld T, van Vuure JK, Frenkel M. Elevated protein requirements in cirrhosis of the liver investigated by whole body protein turnover studies. Clin Sci 1988; 75: 101-107.
191. Swart GR, van den Berg JWO, van Vuure JK, Rietveld T, Wattimena DL, Frenkel M. Minimum protein requirements in liver cirrhosis determined by nitrogen balance measurements at three levels of protein intake. Clin Nutr 1989; 8: 329-336.
192. Tashima L, Cahill GF. Effects of insulin in the toadfish, Opsanus tau. Gen Comp Endocr 1968; 11: 266-71.
193. Tessari P, Inchiostro S, Biolo G, Trevisan R, Fantin G, Marescotti MC, Iori E, Tiengo A, Grepalsi G. Differential effects of hyperinsulinemia and hyperaminoacidemia on leucine-carbon metabolism in vivo. J Clin Invest 1987; 79: 1062-1069.
194. Tobin JS, Roux JF, Soeldner JS. Human fetal insulin response after acute maternal glucose administration during labor. Pediatrics 1969; 44: 668-671.
195. Tweedle DEF, Fitzpatrick GF, Brennan MF, Culebras JM, Wolfe BM, Ball MR, Moore FD. Intravenous amino acids as the sole nutritional substrate. Utilization and metabolism in fasting normal human subjects. Ann Surg 1977; 186: 60-73.
196. Tygstrup N. Determination of the hepatic elimination capacity (Lm) of galactose by single injection. Scand J Clin Lab Invest 1966; 18: 118-125.
197. Unger RH, Orci L. Physiology and pathophysiology of glucagon. Physiological reviews 1976; 56: 778-826.
198. Van der Berghe G, Hue L, Hers HG. Effect of the administration of fructose on the glycogenolytic action of glucagon. Biochem J 1973; 134: 637-645.
199. Vilstrup H. Synthesis of urea after stimulation with amino acids: relation to liver function. Gut 1980; 21: 990-995.
200. Vilstrup H, Bucher D, Krog B, Damgård SE. Elimination of infused amino acids from plasma of control subjects and of patients with cirrhosis of the liver. Eur J Clin Invest 1982; 12: 197-202.
201. Vilstrup H. Effects of glucose on alanine-derived urea synthesis. Clin Physiol 1984; 4: 495-507.
202. Vilstrup H, Iversen J, Tygstrup N. Glucoregulation in acute liver failure. Europ Clin Invest 1986; 16: 193-197.
203. Vilstrup H, Skovgaard LT. Kinetics of hepatic alanine uptake and urea synthesis in pigs. Am J Physiol 1988; 254: G602-G609.
204. Vilstrup H. On urea synthesis regulation in vivo. Dan Med Bull 1989; 36: 415-429.
205. Vilstrup H, Hansen BA, Almdal TP. Glucagon increases hepatic efficacy for urea synthesis. J Hepatol 1990; 10: 46-50 (A).
206. Vilstrup H, Gluud C, Hardt F, Kristensen M, Kohler O, Melgaard B, Hansen BA, Krintel JJ, Schutten HJ, Thomsen AaC. Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy: a double-blind study of 65 patients with cirrhosis. J Hepatol 1990; 10: 291-296 (B).
207. Walser M, Bodenloss LJ. Urea metabolism in man. J Clin Invest 1959; 38: 1617-1626.
208. Wanscher B, Almdal TP, Vilstrup H. Effects of adrenalectomy on urea synthesis in rats. Horm Metab Res 1989; 21: 313-316.
209. Waterlow JC. Observations on the mechanism of adaptation to low protein intakes. Lancet 1968; ii: 1091-1096.
210. Weber FL. The effect of lactulose on urea metabolism and nitrogen excretion in cirrhotic patients. Gastroenterology 1979; 77: 518-523.
211. Winkler K, Keiding S, Tygstrup N. Clearance as a quantitative measure of liver function. In: Preisig R, ed. The liver: quantitative aspects of structure and function. Basel, Karger 1973, 144-155.
212. Wolfe BM, Culebras JM, Sim AJW, Ball MR, Moore FD. Substrate interactions in intravenous feeding. Comparative effects of carbohydrate and fat on amino acid utilization in fasting man. Ann Surg 1977; 186: 518.
213. Wolfe BM, Culebras JM, Aoki TT et al. The effect of glucagon on protein meatbolism in normal man. Surgery 1979; 86: 248-257.
214. Wolfe RR. Measurement of urea kinetics in vivo ny means of a constant tracer infusion of di-15 N-urea. Am J Physiol 1981; 240: E428-E434.
215. Wolfe RR, Shaw JH, Jahoor F, Herndon DN, Wolfe MH. Response to glucose infusion in humans: role of changes in insulin concentration. Am J Physiol 1986; 250: E306-E311.
216. Wolthers T, Grøfte T, Jørgensen JOL, Møller N, Vahl N, Christiansen JS, Vilstrup H. Effects of growth hormone (GH) administration on functional hepatic nitrogen clearance: Studies in normal man and GH-deficient patients. J Clin Endocrinol Metab 1994; 78: 1220-1224.
217. Wolthers T. Grøfte T, Møller N, Vilstrup H. Jørgensen JOL. Effects of long-term growth hormone (GH) and triiodothyronine (T3) on functional hepatic nitrogen clearance in normal man. J Hepatol 1996; 24: 313-319.
218. Woolfson AM, Heatley RV, Allison SP. Insulin to inhibit protein catabolism after injuri. N Engl J Med 1979; 300: 14-17.
219. Zillikens MC, van den Berg JWO, Wattimena JLD, Rietveld T, Swart GR. Nocturnal oral glucose supplementation. The effects on protein metabolism in cirrhotic patients and in healthy controls. J Hepatol 1993; 17: 377-383.