Regulation of the insulin antagonistic protein tyrosine phosphatase 1B by dietary Se studied in growing rats

Protein tyrosine phosphatase I R (PTP1B) is a key enzyme in the counterregulation of insulin signaling, and its physiological modulation depends on 11,0, and glutathione (GSH). Se via(NI peroxidases (GPxs) and its specific metabolism is involved in the removal OF 11202 and in the regulation of GSH I 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 7x7 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 anti by increasing dietary SC 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. (C) 2009 Elsevier Inc. All rights reserved.