Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycolytic and gluconeogenic enzymes in diabetic rats.
Selenium is a trace element that exerts certain insulin-like actions in vitro. In this study, we evaluated its in vivo effects on the glucose homeostasis of rats made diabetic and insulin-deficient by streptozotocin. Na2SeO4 was administered ad libitum in drinking water and/or food for 10 weeks. The elevated plasma glucose levels (approximately 25 mmol/l) and glucosuria (approximately 85 mmol/day) of untreated rats were decreased by 50 and 80%, respectively, by selenate treatment. The beneficial effect of selenate was also evident during oral and intravenous glucose tolerance tests: the integrated glucose responses were decreased by 40-50% as compared to those in untreated rats. These effects were not due to an increase in plasma insulin levels. Compared to non-diabetic rats, pancreatic insulin reserves were reduced by more than 90% in treated and untreated diabetic rats. The hepatic activities and mRNA levels of two key glycolytic enzymes, glucokinase and L-type pyruvate kinase were blunted in diabetic rats. They increased approximately two- to threefold after selenate treatment, to reach 40-75% of the values in non-diabetic rats. In contrast, elevated activity and mRNA levels of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase, were reduced by 40-65% after selenate administration. Since selenate induced a moderate decrease in body weight due to an anorexigenic effect, we checked that there was no improvement of glucose homeostasis or hepatic glucose metabolism in an additional group of calorie-restricted diabetic rats, which was weight-matched with the selenate group. In addition, no obvious toxic side-effects on the kidney or liver were observed in the rats receiving selenate. In conclusion, selenate induces a sustained improvement of glucose homeostasis in streptozotocin-diabetic rats by an insulin-like action, which involves partial correction of altered pretranslational regulatory mechanisms in liver metabolism.
Becker
D J
DJ
Endocrinology and Metabolism Unit, University of Louvain, Brussels, Belgium.
Reul
B
B
Ozcelikay
A T
AT
Buchet
J P
JP
Henquin
J C
JC
Brichard
S M
SM
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D015342:DNA Probes; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005941:Glucokinase / Q000096:biosynthesis; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006019:Glycolysis; D006706:Homeostasis / Q000187:drug effects; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000096:biosynthesis; D011770:Pyruvate Kinase / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D064586:Selenic Acid; D012643:Selenium / Q000378:metabolism; D018036:Selenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D015342:DNA Probes; D007328:Insulin; D018036:Selenium Compounds; D005941:Glucokinase; D011770:Pyruvate Kinase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D012643:Selenium; D064586:Selenic Acid; D005947:Glucose