The present study was performed to examine the mechanism by which selenate ameliorates the insulin sensitivity in type II diabetic dbdb mice. Therefore, 21-adult female dbdb mice were randomly assigned to three experimental groups (0Se, SeIV and SeVI) with seven animals per group. Mice of group 0Se were fed with a selenium-deficient diet (<0.02 mg Se/kg) based on wheat and torula yeast for 8 weeks whereas the mice of groups SeIV (selenite) and SeVI (selenate) were fed with sodium selenite and sodium selenate (up to 35% of the LD(50) for mice in eighth week), in addition to the diet by daily tube feeding. Eight weeks of selenate application led to significantly elevated insulin sensitivity in comparison with selenium deficiency and selenite application. The activity of cytosolic protein tyrosine phosphatases (PTPs) as important negative regulators of insulin signalling was reduced from 53.8% to 22.5% in the liver and skeletal muscle of selenate-treated mice in comparison with the selenium deficient and selenite-treated controls, suggesting an inhibition of PTPs by intermediary selenate metabolites. In an additional in vitro inhibition study, selenate (oxidation state +VI) did not inhibit PTP activity. Selenium metabolites in the oxidation state +IV were found to be the actual inhibitors of PTP activity. In conclusion, the results of the present study show that one possible mechanism by which supranutritional selenate doses enhance insulin sensitivity in type II diabetic dbdb mice is based on the inhibition of PTPS as negative regulators of insulin signalling. Moreover the cellular metabolism of selenate including its intermediary reduction to the oxidation state +IV seems to play a crucial role during this process.

+More

negative ptp activity selenate oxidation state cytosolic protein tyrosine phosphatases ptps insulin signalling reduction

A S, Müller E, Most J, Pallauf,.Effects of a supranutritional dose of selenate compared with selenite on insulin sensitivity in type II diabetic dbdb mice.. 89 (3-6),94-104.

A S, Müller E, Most J, Pallauf,"Effects of a supranutritional dose of selenate compared with selenite on insulin sensitivity in type II diabetic dbdb mice." 89

A S, Müller E, Most J, Pallauf,"Effects of a supranutritional dose of selenate compared with selenite on insulin sensitivity in type II diabetic dbdb mice."