Abstract
Hepatic glycogen catabolism and glycogen levels in rats with chronic arthritis were investigated. At 9:00 a.m., the hepatic glycogen contents of ad libitum fed arthritic and normal rats were 225.5 ± 17.7 and 332.1 ± 28.6 μmol glucosyl units × (g liver)–1, respectively. Food intake of arthritic and normal rats was equal to 100.1 ± 6.7 and 105.0 ± 3.1 mg × (g body w)–1 × (per 24 h)–1, respectively. In isolated perfused livers from normal and arthritic rats the rates of glucose, lactate and pyruvate release were the same when substrate- and hormone-free perfusion was performed. During an infusion period of 20 min glucagon caused an increment in glucose release of 35.3 ± 4.7 μmol × (g liver)–1 in livers from arthritic rats; in the normal condition the corresponding increment was 69.6 ± 5.7 μmol × (g liver)–1. Lactate and pyruvate productions (indicators of glycolysis) were diminished by glucagon in livers from normal rats; in the arthritic condition an initial stimulation was found, followed by a slow decay, which did not result in significant inhibition at the end of the glucagon infusion period (20 min). The actions of cAMP and dibutyryl-cAMP were similar to those of glucagon. It was concluded that livers from arthritic rats show an impaired capacity of releasing glucose under the stimulus of glucagon. This can be partly due to the lower glycogen levels and partly to a smaller capacity of inhibiting glycolysis. Reduction in glycogen levels was not associated with reduction in food intake or failure in the energetic state of the hepatic cells. These changes in glycogen metabolism may be related to reduced gluconeogenic capacity of the livers and/or to production of inflammatory mediators observed in the arthritis disease.
Similar content being viewed by others
References
Roubenoff R, Roubenoff RA, Cannon JG, Kehayias JJ, Zhuang H, Dawson-Hugues B, Dinarello CA, Rosenberg IH: Rheumatoid cachexia: Cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation. J Clin Invest 93: 2379–2386, 1994
Roubenoff R, Freeman LM, Smith DE, Abad LW, Dinarello CA, Kehayias JJ: Adjuvant arthritis as a model of inflammatory cachexia. Arthritis Rheum 40: 534–539, 1997
Caparroz-Assef SM, Bersani-Amado CA, Nascimento EA, Kelmer-Bracht AM, Ishii-Iwamoto EL: Effects of the nonsteroidal anti-inflammatory drug nimesulide on energy metabolism in livers from adjuvant-induced arthritic rats. Res Comm Mol Pathol Pharmacol 99: 93–116, 1998
Fedatto-JÚnior Z, Ishii-Iwamoto EL, Amado CB, Vicentini G, D'Urso-Panerari A, Bracht A, Kelmer-Bracht AM: Gluconeogenesis in the liver of arthritic rats. Cell Biochem Funct 17: 271–278, 1999
Fedatto-JÚnior Z, Ishii-Iwamoto EL, Amado CB, Maciel ERM, Bracht A, Kelmer-Bracht AM: Glucose phosphorylation capacity and glycolysis in the liver of arthritic rats. Inflamm Res 49: 128–132, 2000
Svenson KL, Lundqvist G, Wide L, Hallgren R: Impaired glucose handling in active rheumatoid arthritis: Relationship to the secretion of insulin and counter-regulatory hormones. Metabolism 36: 940–943, 1987
Pearson CM: Development of arthritis, periarthritis and periostitis in rats given adjuvants. Proc Soc Exp Biol Med 91: 95–101, 1956
Scholz R, Bücher T: Hemoglobin-free perfusion of rat liver. In: B. Chance, R.W. Estabrook, J.R. Williamson (eds). Control of Energy Metabolism. Academic Press, New York, 1965, pp 393–414
Keppler D, Decker K: Glycogen. Determination with amyloglucosidase. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 1127–1131
Bergmeyer HU, Bernt E: Glucose determination with glucose oxidase and peroxidase. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 1205–1215
Gutman I, Wahlefeld AW: (+)Lactate determination with lactate dehydrogenase and NAD+. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 1464–1468
Czok R, Lamprecht W: Pyruvate, phosphoenolpyruvate and glycerate-2-phosphate. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 1446–1451
Jaworek D, Gruber W, Bergmeyer U: Adenosine 5′-diphosphate and adenosine 5′-mono-phoshate. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 2127–2131
Lamprecht W, Trautschold I: Adenosine-5′-triphosphate. Determination with hexokinase and glucose-6-phosphate dehydrogenase. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 2101–2110
Kimmig R, Mauch TJ, Kerzl W, Schwabe U, Scholz R: Actions of glucagon on flux rates in perfused rat liver. 1. Kinetics of the inhibitory effect on glycolysis and the stimulatory effect on glycogenolysis. Eur J Biochem 136: 609–616, 1983
Vicentini GE, Constantin J, Lopez CH, Bracht A: Transport of cAMP and synthetic analogs in the perfused rat liver. Biochem Pharmacol 59: 1187–1201, 2000
Bazotte RB, Constantin J, Hell NS, Ishii-Iwamoto EL, Bracht A: The relation between glycolysis inhibition and oxygen uptake stimulation due to glucagon in livers from rats in different metabolic conditions. Cell Biochem Funct 6: 225–230, 1988
Hellerstein MK, Meydani SN, Meydani M, Wu K, Dinarello CA: Interleukin-1-induced anorexia in the rat. Influence of prostaglandins. J Clin Invest 84: 228–235, 1989
Eastegate JÁ, Wood NC, DiGiovine FS, Symons JA, Grinlinton FM, Duff GW: Correlation of plasma interleukin-1 levels with disease activity in rheumatoid arthritis. Lancet ii: 706–709, 1988
Saxne TM, Palladino MA, Heinegard D, Tala N, Wollheim FA: Detection of tumor necrosis factor-α but not tumor necrosis factor-β in rheumatoid arthritis synovial fluids and serum. Arthritis Rheum 31: 1041–1044, 1988
Tracey KJ, Manogue KR, Fong Y, Hesse DG, Nguyen HT, Kuo GC, Beutler B, Cotran RS, Cerami A, Lowry SF: Cachetin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med 167: 1211–1227, 1988
Moldawer LL, Copeland EM: Proinflammatory cytokines, nutritional support, and the cachexia syndrome: Interactions and therapeutic options. Cancer 79: 1828–1839, 1977
Lang CH: Beta-adrenergic blockade attenuates insulin resistance induced by tumor necrosis factor. Am J Physiol 264: R984–R991, 1993
Kuwajima M, Newgards CB, Foster DW, McGarry JD: The glucose-phosphorylating capacity of liver as measured by three independent assays. J Biol Chem 261: 8849–8853, 1986
Kuwajima M, Golden S, Katz J, Unger RH, Foster DW, McGarry JD: Active hepatic glycogen synthesis from gluconeogenic precursors despite high tissue levels of fructose 2,6-bisphosphate. J Biol Chem 261: 2632–2337, 1986
Radziuk J: Sources of carbon in hepatic glycogen synthesis during absorption of an oral glucose load in humans. Fed Proc 41: 110–116, 1982
Friedmann N, Park CR: Early effects of 3′-5′ adenosine monophosphate on the fluxes of calcium and potassium in the perfused liver from normal and adrenolectomized rats. Proc Natl Acad Sci USA 61: 504–508, 1968
Kraus-Friedmann N: Glucagon-stimulated respiration and intracellular Ca2+. FEBS Lett 201: 133–136, 1986
Marques da Silva AC, Kelmer-Bracht AM, Constantin J, Ishii-Iwamoto EL, Yamamoto NS, Bracht A: The influence of Ca2+ on the effects of glucagon on hepatic glycolysis. Gen Pharmacol 30: 655–662, 1998
Somasundaram S, Sadique J: The role of mitochondrial calcium transport during inflammation and the effect of anti-inflammatory drugs. Biochem Med Metab Biol 36: 220–230, 1986
Barrit GJ, Whitehouse MW: Pathobiodynamics: Effect of extrahepatic inflammation on calcium transport and drug metabolism by rat liver mitochondria in vitro. Biochem Med 17: 99–115, 1977
Zentella A, Manogue K, Cerami A: Cachetin/TNF-mediated lactate production in cultured myocytes is linked to activation of a futile substrate cycle. Cytokine 5: 436–447, 1993
Tredget EE, Yu YM, Burini R, Okusawa S, Gelfand JÁ, Dinarello CA, Young VR, Burke JF: Role of interleukin-1 and tumor necrosis factor on energy metabolism in rabbits. Am J Physiol 255: E760–E768, 1988
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fedatto-Júnior, Z., Ishii-Iwamoto, E., Caparroz-Assef, S. et al. Glycogen levels and glycogen catabolism in livers from arthritic rats. Mol Cell Biochem 229, 1–7 (2002). https://doi.org/10.1023/A:1017913124084
Issue Date:
DOI: https://doi.org/10.1023/A:1017913124084