Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-10T15:53:20.057Z Has data issue: false hasContentIssue false
  • English
  • Français

Effect of insulin-like growth factor-I on nitrogen balance and intestinal galactose transport in rats with moderate liver cirrhosis

Published online by Cambridge University Press:  09 March 2007

Marina Núñez ,
Elena Urdaneta  and
Santiago Santidrián
Marina Núñez
Affiliation:
Department of Human Physiology, School of Medicine, University of Navarra, 31008 Pamplona, Spain Department of Internal Medicine, School of Medicine, University of Navarra, 31008 Pamplona, Spain
Elena Urdaneta
Affiliation:
Department of Natural Sciences, School of Agronomy, Public University of Navarra, 31006 Pamplona, Spain
Santiago Santidrián*
Affiliation:
Department of Human Physiology, School of Medicine, University of Navarra, 31008 Pamplona, Spain
*
*Corresponding author: Dr Santiago Santidrián, fax +34 948 425649, email santidrian@unav.es
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The malnutrition caused by liver cirrhosis (LC) often worsens the course of the disease. Patients affected by LC often have a low bioavailability of the anabolic liver peptide insulin-like growth factor (IGF)-I. The present study was undertaken to investigate the effect of low doses of IGF-I on the nutritional status and in vivo jejunal transport of d-galactose in anatomically, pathologically and biochemically confirmed moderate, non-ascitic, cirrhotic rats. LC was experimentally induced in growing rats by inhalation of CCl4 and addition of phenobarbital to drinking water. Both the nutritional status, as evaluated by N balance, and in vivo intestinal transport of d-galactose, were significantly impaired in cirrhotic rats. As compared with healthy rats, administration of 20μg human recombinant IGF-I/kg body weight for 14d to cirrhotic rats significantly improved N balance variables and restored in vivo intestinal transport of the sugar. However, IGF-I had no effect on the steatorrhoea associated with LC. These results suggest that low doses of IGF-I may have beneficial effects on the malnutrition associated with moderate LC.

Keywords

CirrhosisInsulin-like growth factor-INitrogen balanceIntestinal absorption
Type
Research Article
Information
British Journal of Nutrition , Volume 90 , Issue 5 , November 2003 , pp. 929 - 937
Copyright
Copyright © The Nutrition Society 2003

References

Abad, A, Cabre, E, Gonzalez-Huix, F, Dolz, C, Xiol, X & Gassull, MA (1987) Influence of the nutritional status in the prognosis and clinical outcome of hospitalized patients with liver cirrhosis: preliminary report. J Clin Nutr Gastroenterol 2, 63–68.Google Scholar
Ariosto, F, Riggio, O & Cantafora, A et al. (1989) Carbon tetrachloride-induced experimental cirrhosis in the rat. A reappraisal of the model. Eur Surg Res 21, 280–286.CrossRefGoogle Scholar
Bang, S & Hall, M (1992) EZ7: The insulin like growth factors. In Structure and Biological Functions, pp. 151–177 [Hall, M, editor]. Oxford: Oxford University Press.Google Scholar
Biological Council Institute of Biology (1987). Guidelines on the Use of Living Animals in Scientific Investigations. London: BCIB.Google Scholar
Butler, AA, Yakar, S & Le Roith, D (2002) Insulin like growth factor-I: compartmentalization within the somatotropic axis? News Physiol Sci 17, 82–85.Google ScholarPubMed
Cabre, E & Gassull, MA (1999) Nutritional issues in cirrhosis and liver transplantation. Cur Opin Clin Nutr Metab Care 2, 373–380.Google Scholar
Campillo, B, Bories, PN, Devanlay, M, Somner, F, Wirquin, E & Fonet, P (1992) The thermogenic and metabolic effects of food in liver cirrhosis: consequences on the storage of nutrients and the hormonal contrarregulatory response. Metab Clin Exp 41, 476–482.Google Scholar
Canfriez, A, Rendig, P, Urbain, D, Goldstein, J & Copinschi, G (1991) Insulin-like growth factor-I: a good indicator of functional hepatocellular capacity in alcoholic liver cirrhosis. J Endocrinol Invest 14, 317–321.CrossRefGoogle Scholar
Carro, E, Trejo, LJ, Gomez-Isla, T, LeRoith, D & Torres-Aleman, I (2002) Serum insulin-like growth factor-I regulates brain amyloid- β levels. Nature 8, 1390–1397.Google ScholarPubMed
Castilla, I, Calvo, A, Diez, N, Pascual, M, Quiroga, J & Prieto, J (2000) Low doses of insulin-like growth factor-I revert the testicular atrophy associated to advanced liver cirrhosis. Hepatology 31, 592–600.CrossRefGoogle Scholar
Castilla, I, García, M, Muguerza, B, Perez, R, Santidrían, S & Prieto, J (1997 a) Hepatoprotective effects of insulin-like growth factor-I in rats with carbon tetrachloride-induced cirrhosis. Gastroenterology 113, 1682–1691.Google Scholar
Castilla, I, Prieto, J, Urdaneta, E et al. (1997 b) Impaired intestinal sugar transport in cirrhotic rats: correction by low doses of insulin-like growth factor-I. Gastroenterology 113, 1180–1187.CrossRefGoogle Scholar
Corkins, MR, Park, JH, Davis, DV, Slentz, DH & MacDonald, RG (1999) Regulation of the insulin like growth factor axis by increasing cell number in intestinal epithelial (IEC-6) cells. Growth Horm IGF Res 9, 414–424.Google Scholar
Chatamra, K & Proctor, E (1981) Phenobarbitone-induced enlargement of the liver in the rats: its relationship to carbon tetrachloride-induced cirrhosis. Br J Exp Pathol 62, 283–288.Google Scholar
Donaghy, A, Ross, R, Gimson, A, Hughes, SC, Holly, J & Williams, R (1995) Growth hormone, insulin-like growth factor binding proteins 1 and 3 in chronic liver disease. Hepatology 21, 680–688.Google ScholarPubMed
Donaghy, AJ, Delhanty, PJ, Ho, KK, Willians, R & Baxter, RC (2002) Regulation of the GH receptor/binding protein, insulin-like growth factor ternary complex system in human cirrhosis. J Hepatol 36, 751–758.CrossRefGoogle ScholarPubMed
Dube, C, Vallieres, S, Ethier, C, Benbrahim, N, Tremblay, C & Gascon-Barre, M (1991) Micronodular cirrhosis, hepatocytes retain a normal C-25 hydroxylation capacity toward vitamin D 3 : a study using the rat with carbon tetrachloride-induced cirrhotic model. Hepatology 13, 489–499.Google ScholarPubMed
Ebeling, PR, Jones, JD, O'Fallon, WM, Jones, CH & Riggs, BL (1993) Short-term effects of recombinant human insulin-like growth factor-I on bone turnover in normal women. J Clin Endocrinol Metab 77, 1384–1387.Google Scholar
Epstein, M (1990) Hepatology: A Textbook of Liver Disease, [Zakim, D, editor]. Philadelphia, PA: WB Saunders Company.Google Scholar
Felber, JP & Galay, A (1995) Regulation of nutrient metabolism and energy expenditure. Metabolism 44, 4–9.Google Scholar
Fujiwara, K, Ogata, I, Otha, Y et al. (1988) Decreased collagen accumulation by a prolyl hydroxylase inhibitor in pig serum-induced fibrotic rat liver. Hepatology 8, 804–807.CrossRefGoogle ScholarPubMed
Greco, AV, Mingrone, G, Benedetti, G, Capristo, E, Tataranni, PA & Gasbarrini, G (1998) Daily energy and substrate metabolism in patients with cirrhosis. Hepatology 27, 346–350.CrossRefGoogle ScholarPubMed
Hattori, N, Kurahachi, H, Ikekubo, Ket al. (1992) Serum growth hormone-binding protein, insulin-like growth factor-I and growth hormone in patients with liver cirrhosis. Metab Clin Exper 41, 377–381.Google Scholar
Hobler, SC, Willians, AB, Fischer, JE & Hasselgren, PO (1998) IGF-I stimulates protein synthesis but does not inhibit protein breakdown in muscle from septic rats. Am J Physiol 274, R571–R576.Google Scholar
Holt, RI, Baker, AJ, Jones, JS & Miell, JP (1998) The insulin-like growth factor and binding protein axis in children with end-stage liver disease before and after orthotopic liver transplantation. Pediatr Transplant 2, 76–84.Google ScholarPubMed
Imai, Y, Moralez, A, Andag, U, Clarke, JB, Busby, J & Clemmons, DR (2000) Substitutions for hydrophobic amino acids in the N terminal domains of IGFBP-3 and 5 markedly reduce IGF-I binding and alter their biological actions. J Biol chem 275, 9327–9330.Google Scholar
Jacob, R, Barret, E, Plave, G, Fagin, KD & Sherwin, RS (1989) Acute effects of insulin-like growth factor-I on glucose and amino acid metabolism in the awake fasted rat: comparison with insulin. J Clin Invest 83, 1717–1723.CrossRefGoogle ScholarPubMed
Johnston, AL & File, SE (1989) Sodium phenobarbitone reverses the anxiogenic effect of compounds acting at three different central sites. Neuropharmacology 28, 83–88.Google Scholar
Kondrup, J, Nielsen, K & Hamberg, O (1992) Nutritional therapy in patients with liver cirrhosis. Eur J Clin Nutr 46, 239–246.Google ScholarPubMed
Krähenbuhl, S, Weber, FL & Brass, EP (1991) Decreased hepatic glycogen content and accelerated response to starvation in rats with carbon tetrachloride-induced cirrhosis. Hepatology 14, 1189–1195.Google Scholar
Longwell, AC & Stiles, SS (1968) Removal of yolk from oyster eggs by Soxhlet extraction for clear chromosome preparations. Stain Technol 43, 63–68.Google Scholar
Lupu, F, Terwilliger, JD, Lee, K, Segre, GV & Efstratiadis, A (2001) Roles of growth hormone and insulin like growth factor I in mouse postnatal development. Dev Biol 229, 141–162.Google Scholar
McCullough, AJ (1992) Complications of Chronic Liver Disease, McCullough, AJ, editor]. St Louis, MO: Mosby Year Book Inc.Google Scholar
McCullough, AJ & Tavill, AS (1991) Disordered energy and protein metabolism in liver disease. Semin Liver Dis 11, 265–277.Google Scholar
MacDonald, RS (1999) The role of insulin-like growth factors in small intestinal cell growth and development. Horm Metab Res 31, 103–113.CrossRefGoogle ScholarPubMed
Marchesini, G, Zoli, M, Dondi, C & Pisi, E (1982) Anticatabolic effect of branched-chain amino acid-enriched solutions in patients with liver cirrhosis. Hepatology 2, 480–485.Google ScholarPubMed
Maxvold, NJ, Smoyer, WE, Custer, JR & Bunchman, TE (2000) Amino acid loss and nitrogen balance in critically ill children with acute renal failure: a prospective comparison between classic hemofiltration and hemofiltration with dialysis. Crit Care Med 28, 1161–1165.Google Scholar
Mendenhall, CL, Anderson, S, Weesner, RE, Goldberg, SJ & Crolic, KA (1984) Protein–calorie malnutrition associated with alcoholic hepatitis. Am J Med 76, 211–222.Google Scholar
Merli, M, Caschera, M, Piat, C, Pinto, G, Diofebi, M & Riggio, O (1992) The effect of lactulose and lactitol administration on fecal fat excretion in patients with liver cirrhosis. J Clin Gastroenterol 15, 125–157.Google Scholar
Mezey, E (1978) Liver disease and nutrition. Gastroenterology 74, 770–783.CrossRefGoogle ScholarPubMed
Moller, S, Gronbaek, M, Main, K, Becker, U & Skakkebaek, EN (1993) Urinary growth hormone (U-GH) excretion and serum insulin-like growth factor 1 (IGF-1) in patients with alcoholic cirrhosis. J Hepatol 17, 315–320.Google Scholar
Moller, S, Juul, A, Becker, U, Flyvbjerg, A, Skakkebaek, EN & Henriksen, JH (1995) Concentrations, release and disposal of IGF-binding proteins (IGFBP), IGF-I, and growth hormone in different vascular beds in patients with cirrhosis. J Clin Endocrinol Metab 80, 1148–1157.Google ScholarPubMed
Muguerza, B, Picardi, A, Quiroga, J, Castilla, I, Santidrian, S & Prieto, J (1995) Efecto de la administración de dosis bajas del factor de crecimiento análogo a la insulina (IGF-I) sobre la cantidad de colágeno hepático en ratas con cirrosis hepatica (Effect of low doses of insulin-like growth factor I (IGF-I) on the hepatic collagen in rats with liver cirrhosis). Gastroenterol Hepatol 18, 291–292.Google Scholar
Mullen, KD & McCullough, AJ (1989) Problems with animal models of chronic liver disease: suggestions for improvement in standardization. Hepatology 9, 500–503.CrossRefGoogle ScholarPubMed
Müller, MJ (1998) Hepatic energy and substrate metabolism: a possible metabolic basis for early nutritional support in cirrhotic patients. Nutrition 14, 30–38.CrossRefGoogle ScholarPubMed
Müller, MJ, Lantz, HU, Plogmann, B, Bürger, M, Körber, J & Schmidt, FW (1992) Energy expenditure and substrate oxidations in patients with cirrhosis: the impact of causes, clinical staging and nutritional state. Hepatology 15, 782–794.CrossRefGoogle ScholarPubMed
Muñoz, SJ (1991) Nutritional therapies in liver disease. Semin Liver Dis 11, 278–291.CrossRefGoogle ScholarPubMed
National Academy of Sciences (1991) The Guiding Principles for Research Involving Animals, Washington, DC: National Institute of Health.Google Scholar
Navarro-Alarcon, M & López, MC (2000) Essentiality of selenium in the human body: relationship with different diseases. Sci Total Environ 249, 347–371.CrossRefGoogle ScholarPubMed
O'Keefe, SJD, El-Zayadi, AR, Carraher, TE, Davis, M & Williams, R (1980) Malnutrition and immunoincompetence in patients with liver disease. Lancet 2, 615–617.Google Scholar
Pascual, M, Castilla, I, Urdaneta, E et al. (2000) Altered intestinal transport of amino acids in cirrhotic rats: the effect of insulin-like growth factor-I. Am J Physiol 279, G319–G324.Google Scholar
Petrides, AS & Defronzo, RA (1989) Glucose metabolism in cirrhosis: A review with some perspectives for the future. Diabetes Metab Rev 5, 691–709.Google Scholar
Picardi, A, Oliveira, AC, Muguerza, B et al. (1997) Low doses of insulin-like growth factor-I improve nitrogen retention and food efficiency in rats with early cirrhosis. J Hepatol 26, 191–202.Google Scholar
Plaa, GL & Charbonneau, M (1994) Principles and Methods of Toxicology [Tardiff, RG, editor]. New York: Raven Press Ltd.Google Scholar
Ponz, F, Ilundain, A & Lluch, M (1979) Method for successive absorptions with intestinal perfusion in vivo. Rev Esp Fisiol 35, 97–104.Google Scholar
Potter, SM (1995) Overview of proposed mechanisms for hypocholesterolemic effect of soy. J Nutr 125, 606–611.Google ScholarPubMed
Ross, RJM, Chew, SL, D'Souza Li, L, Yateman, M, Rodriguez-Arnao, J & Gimson, A (1996) Expression of IGF-I and IGF-binding protein genes in cirrhotic liver. J Endocrinol 149, 209–216.Google Scholar
Russell-Jones, DL, Umplebey, AM, Henessy, TR et al. (1994) Use of leucine clamp to demonstrate that insulin-like growth factor-I actively stimulates protein synthesis in normal humans. Am J Physiol 267, E591–E598.Google ScholarPubMed
Salvioli, G, Carati, L & Lugli, R (1990) Steatorrhoea in cirrhosis: effect of ursodeoxycholic acid administration. J Int Med Res 18, 289–297.Google Scholar
Schalah, DS, Kalayoghu, M, Pirsch, JD, Yang, H, Raslich, M & Rajpal, S (1998) Serum insulin-like growth factors and their binding proteins in patients with hepatic failure and after liver transplantation. Metabolism 47, 200–206.Google Scholar
Schimpff, RM, Lebrec, D & Donadieu, M (1977) Somatomedin production in normal adults and cirrhotic patients. Acta Endocrinol 86, 355–362.Google Scholar
Scholmerich, J, Krauss, E, Wietholtz, H, Kottgen, E, Lohle, E & Gerok, W (1987) Bioavailability of zinc from zinc–histidine complexes. Studies on patients with liver cirrhosis and the influence of the time of application. Am J Clin Nutr 45, 1487–1491.Google Scholar
Smith, WJ, Underwood, LE & Clemmons, DR (1995) Effects of caloric or protein restriction on IGF-I and IGF-binding proteins in children and adults. J Clin Endocrinol Metab 80, 443–449.Google Scholar
Zoli, M, Marchesini, G, Dondi, C & Pisi, E (1982) Myofibrilar protein catabolic rates in cirrhotic patients with and without muscle wasting. Clin Sci 62, 683–686.Google Scholar