Metabolic effect of sodium selenite: insulin-like inhibition of glucagon-stimulated glycogenolysis in the isolated perfused rat liver.
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 mumol/L at infusion of 10, 50, 100, and 500 mumol/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 mumol/L: 0.21 +/- 0.09 mumol.min-1.g-1 liver; P < .05 vs. zero time), while it was transiently increased by 500 mumol/L sodium selenite (1.11 +/- 0.18 mumol.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 mumol/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 mumol/L), but not of low-dose selenite (10 mumol/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.
Roden
M
M
Department of Internal Medicine III, University of Vienna, Austria.
Prskavec
M
M
Fürnsinn
C
C
Elmadfa
I
I
König
J
J
Schneider
B
B
Wagner
O
O
Waldhäusl
W
W
D000818:Animals; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000096:biosynthesis; D006003:Glycogen / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D008297:Male; D009994:Osmolar Concentration; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology*
D007328:Insulin; D006003:Glycogen; D005934:Glucagon; D012643:Selenium; D018038:Sodium Selenite; D005947:Glucose