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Diabetologia

, Volume 39, Issue 1, pp 3–11 | Cite as

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

  • D. J. Becker
  • B. Reul
  • A. T. Ozcelikay
  • J. P. Buchet
  • J. -C. Henquin
  • S. M. Brichard
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Summary

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 (~ 25 mmol/l) and glucosuria (~ 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 ~ 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.

Key words

Selenium glycolytic enzymes gluconeogenic enzymes gene expression streptozotocin-diabetic rats 

Abbreviations

GK

Glucokinase

l-PK

l-type pyruvate kinase

PEP

phosphoenolpyruvate

PEPCK

phosphoenolpyruvate carboxykinase

C

non-diabetic control rats

D

untreated diabetic rats

WM

weight-matched diabetic rats

Se

selenatetreated diabetic rats

OGTT

oral glucose tolerance test

IV-GTT

intravenous glucose tolerance test

STZ

streptozotocin

SSC

sodium saline citrate

SSPE

sodium saline phosphate ethylenediamine tetraacetic acid

GLUT2

glucose transporter isoform 2

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • D. J. Becker
    • 1
  • B. Reul
    • 1
  • A. T. Ozcelikay
    • 1
  • J. P. Buchet
    • 2
  • J. -C. Henquin
    • 1
  • S. M. Brichard
    • 1
  1. 1.Endocrinology and Metabolism Unit, Faculty of MedicineUniversity of LouvainBrusselsBelgium
  2. 2.Industrial Toxicology Unit, Faculty of MedicineUniversity of LouvainBrusselsBelgium

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