Regulation of the insulin antagonistic protein tyrosine phosphatase 1B by dietary Se studied in growing rats.
Protein tyrosine phosphatase 1B (PTP1B) is a key enzyme in the counterregulation of insulin signaling, and its physiological modulation depends on H2O2 and glutathione (GSH). Se via GSH peroxidases (GPxs) and its specific metabolism is involved in the removal of H2O2 and in the regulation of GSH metabolism. Recent results from animal trials and epidemiological studies with humans have shown that a high GPx1 activity or a permanent surplus of Se may promote the development of obesity and diabetes. Our nutrition physiological study with 7 x 7 growing rats was carried out to examine if PTP1B is modulated by Se supplements and, thus, may represent one trigger mediating these undesirable metabolic effects of Se. One group of rats was fed an Se-deficient diet for 8 weeks. The diets of the other six groups contained Se as selenite or selenate according to the recommendations (0.20 mg/kg diet) and at two supranutritional levels (1.00 and 2.00 mg/kg diet). All Se-supplemented animals featured a significantly higher body weight (6-14%) compared to their Se-deficient companions. Expression and activity of GPx1 in the liver of Se supplemented animals was 10- and 70-fold higher compared to Se deficiency. The detailed study of PTP1B regulation using an enzymatic assay and Western Blot analysis with an antibody against protein glutathionylation revealed that PTP1B was significantly up-regulated by both a maximization of GPx1 activity and by increasing dietary Se supply, reducing its inhibition via glutathionylation. Selenate effected a stronger PTP activation compared to selenite. In conclusion, our results suggest that the modulation of PTP1B activity may represent one plausible mechanism by which a long-term intake of Se supplements exceeding the requirements can promote the development of obesity and diabetes and needs further intensive investigation.
Mueller
Andreas S
AS
Department of Animal Nutrition and Nutritional Physiology, Interdisciplinary Research Centre, Justus Liebig University Giessen, Giessen D-35392, Germany. andreas.s.mueller@agrar.uni-giessen.de
Bosse
Astrid C
AC
Most
Erika
E
Klomann
Sandra D
SD
Schneider
Sandra
S
Pallauf
Josef
J
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009751:Nutritional Requirements; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000008:administration & dosage* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D007328:Insulin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012643:Selenium