Metabolic effect of sodium selenite: Insulin-like inhibition of glucagon-stimulated glycogenolysis in the isolated perfused rat liver
Corresponding Author
Michael Roden MD
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, Austria
Department of Internal Medicine, Yale University Medical School, Fitkin I; 333 Cedar Street, New Haven, CT 06520–8020===Search for more papers by this authorMartin Prskavec
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, Austria
Search for more papers by this authorClemens Fürnsinn
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, Austria
Search for more papers by this authorIbrahim Elmadfa
Institute of Nutrition, University of Vienna, Austria
Search for more papers by this authorJürgen König
Institute of Nutrition, University of Vienna, Austria
Search for more papers by this authorBarbara Schneider
Institute of Medical Statistics, University of Vienna, Austria
Search for more papers by this authorOswald Wagner
Department of Clinical Chemistry and Laboratory Diagnostics, University of Vienna, Austria
Search for more papers by this authorWerner Waldhäusl
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, Austria
Search for more papers by this authorCorresponding Author
Michael Roden MD
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, Austria
Department of Internal Medicine, Yale University Medical School, Fitkin I; 333 Cedar Street, New Haven, CT 06520–8020===Search for more papers by this authorMartin Prskavec
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, Austria
Search for more papers by this authorClemens Fürnsinn
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, Austria
Search for more papers by this authorIbrahim Elmadfa
Institute of Nutrition, University of Vienna, Austria
Search for more papers by this authorJürgen König
Institute of Nutrition, University of Vienna, Austria
Search for more papers by this authorBarbara Schneider
Institute of Medical Statistics, University of Vienna, Austria
Search for more papers by this authorOswald Wagner
Department of Clinical Chemistry and Laboratory Diagnostics, University of Vienna, Austria
Search for more papers by this authorWerner Waldhäusl
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, Austria
Search for more papers by this authorAbstract
Selenium, an essential trace element, has been shown to decrease plasma glucose concentrations of diabetic rats. To study the short-term effects of selenium on hepatic carbohydrate metabolism, isolated perfused livers of fed Sprague-Dawley rats were continuously infused with sodium selenite for 90 minutes. This resulted in an immediate elevation of selenium in the effluent perfusate (3.3 ± 0.1, 16.1 ± 0.4, 30.3 ± 1.6, and 118.9 ± 0.8 μmol/L at infusion of 10,50, 100, and 500 μmol/L sodium selenite, respectively). Basal hepatic glucose production decreased in a dose-dependent manner within 60 minutes of low-dose sodium selenite infusion (10: 0.60 ± 0.20, 50: 0.21 ± 0.40, and 100 ümol/L: 0.21 ± 0.09 μmol/L · min−1 · g−1 liver; P < .05 vs. zero time), while it was transiently increased by 500 μmol/L sodium selenite (1.11 ± 0.18 μmol · min<1> · g−1 liver; P < .05). Glucagon-stimulated glycogenolysis was suppressed by 50% (P < .05) at 1.8 nmol/ L insulin and by 90% (P < .001) at 10 μmol/L sodium selenite. That selenium concentration did not affect glutathione peroxidase activities in liver and perfusate erythrocytes within 60 minutes. Toxic effects of high-dose selenite (500 μmol/L), but not of low-dose selenite (10 μmol/L) infusion, were indicated by increased hepatic glucose (P < .05), lactate (P < .01), and lactate dehydrogenase (P < .001) release as well as histologically by degeneration and necrosis of periportal hepatocytes. In conclusion, low-dose selenite exerts a potent insulinlike effect on hepatic glycogenolysis in vitro by counteracting glucagon action, whereas high-dose selenite may severely impair liver function. (HEPATOLOGY 1995; 22:169–174.)
References
- 1 Van Vleet JF, Ferrans VJ. Etiologic factors and pathologic alter ations in selenium-vitamin E deficiency and excess in animals and humans. Biol Trace Elem Res 1992; 33: 1–2.
- 2 Ge K, Yang G. The epidemiology of selenium deficiency in the etiological study of endemic diseases in China. Am J Clin Nutr 1993; 57 (suppl): 259S–263S.
- 3 Arthur JR, Nicol F, Beckett GJ. Selenium deficiency, thyroid hormone metabolism, and thyroid hormone deiodinases. Am J Clin Nutr 1993; 57 (Suppl): 236S–239S.
- 4 Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science 1973; 179: 588–590.
- 5 Berry MJ, Banu L, Larsen PR. Type I iodothyronine deiodinase is a selenocysteine-containing enzyme. Nature 1991; 349: 438–440.
- 6 McNeill JH, Delgatty HL, Battell ML. Insulinlike effects of sodium selenate in streptozocin-induced diabetic rats. Diabetes 1991; 40: 1675–1678.
- 7 Ezaki O. The insulin-like effects of selenate in rat adipocytes. J Biol Chem 1990; 265: 1124–1128.
- 8 Shechter Y, Karlish SJD; Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions. Nature 1980; 284: 556–558.
- 9 Heyliger CE, Tahiliani AG, McNeill JH. Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 1985; 227: 1474–1476.
- 10 Brichard SM, Bailey CJ, Henquin J-C, Marked improvement of glucose homeostasis in diabetic ob/ob mice given oral vanadate. Diabetes 1990; 39: 1326–1332.
- 11 Roden M, Liener K, Fürnsinn C, Prskavec M, Nowotny P, Steffan I, Vierhapper H, Waldhäusl W. Non-insulin-like action of sodium orthovanadate in the isolated perfused liver of fed, non diabetic rats. Diabetologia 1993; 36: 602–607.
- 12 Rall TW, Sutherland EW, Berthert J. The relationship of epinephrine and glucagon to liver phosphorylase. J Biol Chem 1956; 224: 463–475.
- 13 Roden M, Vierhapper H, Liener K, Waldhäusl W. Endothelin-1 stimulated glucose production in vitro in the isolated perfused rat liver. Metabolism 1992; 41: 290–295.
- 14 Burton SD, Ishida T. Effect of insulin on potassium and glucose movement in perfused rat liver. Am J Physiol 1965; 209: 1145–1151.
- 15 Roden M, Liener K, Fürnsinn C, Hollenstein U, Vierhapper H, Waldhäusl W. Effects of islet amyloid polypeptide on hepatic insulin resistance and glucose production in the isolated perfused rat liver. Diabetologia 1992; 35: 116–120.
- 16 Brada D, Kerjaschki D, Roth J. Cell type-specific post-Golgi apparatus localization of a “resident” endoplasmic reticulum glycoprotein, glucosidase II. J Cell Biol 1990; 110: 309–318.
- 17 Speitling A, Hüppe R, Kohlmeier M, et al. In: W Kübler, HJ Anders, W Heeschen, M Kohlmeier, eds. Methodenhandbuch der verbundstudie ernährungserhebung und risikofaktorenanalytik. Vol 1. Niederkleen: Wiss. Fachverlag Dr Fleck, 1992: 129–132.
- 18 Beutler E. Glutathione-peroxidase. In: E Beutler, ed. Red cell metabolism. A manual of biochemical methods. New York: Grune & Stratton, 1984: 74.
- 19 Lowry OH, Rosebrough N, Farr AL, Randall RJ. Protein measurement with the folinphenol reagent. J Biol Chem 1951; 193: 265–275.
- 20 Exton JH, Lewis SB, Ho RJ, Robinson GA, Park CR. The role of cyclic AMP in the interaction of glucagon and insulin in the control of liver metabolism. Ann NY Acad Sci 1971; 185: 85–100.
- 21 Abdel Rahim AG, Arthur JR, Mills CF. Effects of dietary copper, cadmium, iron, molybdenum and manganese on selenium utilization by the rat. J Nutr 1986; 110: 403–411.
- 22 Thomson CD, Steven SM, van Rij AM, Wade CR, Robinson MF. Selenium and vitamin E supplementation: activities of glutathione peroxidase in human tissues. Am J Clin Nutr 1988; 48: 316–323.
- 23 Potmis RA, Nonavinakere VK, Rasekh HR, Early JL 2d. Effect of selenium (Se) on plasma ACTH, beta-endorphin, corticosterone and glucose in rat: influence of adrenal enucleation and metyrapone treatment. Toxicology 1993; 79: 1–9.
- 24 Souness JE, Stouffer JE. The effect of selenium-deficiency on rat fat-cell glucose oxidation. Biochem J 1983; 214: 471–477.
- 25 Ueki H, Ohkura Y, Tominga N, Sera M, Morita T. Increase in lipoprotein lipase activity in isolated rat fat pads by selenate: comparison with vanadate. J Pharmacobio-Dyn 1991; 14: 130.
- 26 Bell RR, Nonavinakere VK, Soliman MR, Early JL 2d. Effect of in vitro treatment of rat hepatocytes with selenium, and/or cadmium on cell viability, glucose output, and cellular glutathione. Toxicology 1991; 69: 111–119.
- 27 Tamura S, Brown TA, Whipple JH, et al. A novel mechanism of the insulin-like effects of vanadate on glycogen synthesis in isolated rat adipocytes. J Biol Chem 1984; 259: 6650–6658.
- 28 Bosch F, Arino J, Gomez-Foix AM, Guinovart JJ. Glycogenolytic, noninsulin-like effects of vanadate on rat hepatocyte glycogen synthase and phosphorylase. J Biol Chem 1987; 262: 218–222.
- 29 Crary EJ, McCarty MF. Potential clinical applications for high-dose nutritional antioxidants. Medical Hypothesis 1984; 13: 77–98.
- 30 Chung A-S, Maines MD. Effect of selenium on glutathione metabolism. Induction of gamma-glutamylcysteine synthase and glutathione reductase in the rat liver. Biochem Pharmacol 1981; 30: 3217–3223.
- 31 Tho LL, Candlish JK, Thai AC. Correlates of diabetic markers with erythrocytic enzymes decomposing reactive oxygen species. Ann Clin Biochem 1988; 25: 426–431.
- 32 Nath N, Chari SN, Rathi AB. Superoxide dismutase in diabetic polymorphonuclear leucocytes. Diabetes 1984; 33: 586–589.
- 33 Godin DV, Wohaieb SA, Garnett ME, Goumeniouk AD. Antioxidant enzyme alterations in experimental and clinical diabetes. Mol Cell Biochem 1988; 84: 223–231.
- 34 Ward NJ, Pien B. Trace element concentration in blood plasma from diabetic patients and normal individuals. Biol Trace Elem Res 1984; 6: 469–487.
- 35 Schlienger JL, Grunenberger F, Maier EA, Simon C, Chabrier G, Leroy MJ. Perturbation des oligoelements plasmatiques dans le diabete. Relation avec l'equilibre glycemique. Presse Medical 1988; 17: 1076–1079.
- 36 Dutta SK, Miller PA, Greenberg LB, Levander OA. Selenium and acute alcoholism. Am J Clin Nutr 1983; 38: 713–718.
- 37 Thuluvath PJ, Triger DR. Selenium in chronic liver disease. J Hepatol 1992; 14: 176–182.