Dj. Becker et al., ORAL SELENATE IMPROVES GLUCOSE-HOMEOSTASIS AND PARTLY REVERSES ABNORMAL EXPRESSION OF LIVER GLYCOLYTIC AND GLUCONEOGENIC ENZYMES IN DIABETIC RATS, Diabetologia, 39(1), 1996, pp. 3-11
Citations number
42
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Selenium is a trace element that exerts certain insulin-like actions i
n vitro. In this study, we evaluated its in vivo effects on the glucos
e homeostasis of rats made diabetic and insulin-deficient by streptozo
tocin. Na2SeO4 was administered ad libitum in drinking water and/or fo
od for 10 weeks. The elevated plasma glucose levels (similar to 25 mmo
l/l) and glucosuria (similar to 85 mmol/day) of untreated rats were de
creased by 50 and 80 %, respectively, by selenate treatment. The benef
icial effect of selenate was also evident during oral and intravenous
glucose tolerance tests: the integrated glucose responses were decreas
ed by 40-50 % as compared to those in untreated rats. These effects we
re not due to an increase in plasma insulin levels, Compared to non-di
abetic rats, pancreatic insulin reserves were reduced by more than 90
% in treated and untreated diabetic rats. The hepatic activities and m
RNA levels of two key glycolytic enzymes, glucokinase and L-type pyruv
ate kinase were blunted in diabetic rats. They increased similar to tw
o- to threefold after selenate treatment, to reach 40-75 % of the valu
es in non-diabetic rats. In contrast, elevated activity and mRNA level
s of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase, were
reduced by 40-65 % after selenate administration. Since selenate indu
ced a moderate decrease in body weight due to an anorexigenic effect,
we checked that there was no improvement of glucose homeostasis or hep
atic glucose metabolism in an additional group of calorie-restricted d
iabetic rats, which was weight-matched with the selenate group. In add
ition, no obvious toxic side-effects on the kidney or liver were obser
ved in the rats receiving selenate. In conclusion, selenate induces a
sustained improvement of glucose homeostasis in streptozotocin-diabeti
c rats by an insulin-like action, which involves partial correction of
altered pretranslational regulatory mechanisms in liver metabolism.