Metabolic effect of sodium selenite: Insulin‐like inhibition of glucagon‐stimulated glycogenolysis in the isolated perfused rat liver

• Published in: Hepatology (Baltimore, Md.) Md.), 1995-07, Vol.22 (1), p.169-174
• Main Authors: Roden, Michael, Prskavec, Martin, Fürnsinn, Clemens, Elmadfa, Ibrahim, König, Jürgen, Schneider, Barbara, Wagner, Oswald, Waldhäusl, Werner
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Glucagon - pharmacology; Glucose - biosynthesis; Glycogen - metabolism; In Vitro Techniques; Insulin - pharmacology; Liver - drug effects; Liver - metabolism; Liver - physiology; Male; Medical sciences; Osmolar Concentration; Perfusion; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Selenium - metabolism; Sodium Selenite - pharmacology; Toxicity: digestive system
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.1840220127

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 · 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.)