Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycolytic and gluconeogenic enzymes in diabetic rats.

Abstract

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.

• Authors: D J Becker, B Reul, A T Ozcelikay, J P Buchet, J C Henquin, S M Brichard
• Journal: Diabetologia (Diabetologia) Vol. 39 Issue 1 Pg. 3-11 (Jan 1996) ISSN: 0012-186X [Print] Germany
• PMID: 8720597 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• DNA Probes
• Insulin
• Selenium Compounds
• Glucokinase
• Pyruvate Kinase
• Phosphoenolpyruvate Carboxykinase (GTP)
• Selenium
• Selenic Acid
• Glucose

Topics

• Administration, Oral
• Animals
• Blood Glucose (drug effects, metabolism)
• Blotting, Northern
• Body Weight (drug effects)
• DNA Probes
• Diabetes Mellitus, Experimental (blood, drug therapy, metabolism)
• Gene Expression (drug effects)
• Glucokinase (biosynthesis)
• Gluconeogenesis
• Glucose (metabolism)
• Glucose Tolerance Test
• Glycolysis
• Homeostasis (drug effects)
• Insulin (blood)
• Islets of Langerhans (drug effects, physiology, physiopathology)
• Liver (drug effects, enzymology)
• Male
• Phosphoenolpyruvate Carboxykinase (GTP) (biosynthesis)
• Pyruvate Kinase (biosynthesis)
• Rats
• Rats, Wistar
• Selenic Acid
• Selenium (metabolism)
• Selenium Compounds (administration & dosage, pharmacology)