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

Selenium and diabetes - evidence from animal studies

“…More specifically, the Se-overdosed pigs had >50% plasma insulin levels than the Se-adequate pigs to maintain similar plasma glucose concentrations, indicating an early sign of insulin resistance. Unlike rats [58][59][60], pigs fed the high-Se diet (3 mg of Se/kg of diet) did not develop hyperlipidemia compared with those fed 0.3 mg of Se/kg of diet. Meanwhile, Pinto et al [63] reported that after 16 weeks of intervention, fasting plasma insulin and cholesterol levels were increased in pigs fed 0.50 mg of Se/kg of diet (as Se-yeast) compared with those fed 0.17 mg of Se/kg of diet, although fasting glucose concentrations did not differ between the two groups.…”

“…This type of ROS elevation is implicated in the molecular mechanisms for the insulin-like effects of Se, as elevated H 2 O 2 may activate insulin signaling by an oxidative inhibition of PTP-1b [82][83][84][85]. Meanwhile, a high selenite diet (1.0-2.0 mg of Se/kg of diet) [59] resulted in a lower GSSG/GSH ratio in the rat liver, compared with a Se adequate diet (0.2 mg of Se/kg of diet). This antioxidant effect was in accordance with increased plasma GPx3 activity by high Se over adequate Se supplements, although the high selenite diet had no effect on the activities of GPx1 and SOD in the liver, and even decreased catalase activity.…”

“…While the elevated tissue GPx activity could attenuate insulin sensitivity by diminishing oxidative inhibition of PTP1b, Mueller et al [59] reported a high Se diet (1.0-2.0 mg of Se/kg of diet as selenite or selenate) markedly elevated liver PTP1b activity in rats through reduction of glutathionylation of PTP1b, compared with the Se adequate diet (0.2 mg of Se/kg of diet). Apparently, this elevation of PTP1b activity attenuated insulin-stimulated tyrosine phosphorylation of IRS, resulting in impairment of insulin signaling.…”

“…First, many of the past animal studies used diabetic animals [29][30][31][32][33][34][35][36][37][38][39], but the present studies have been conducted in normal animals [53,[57][58][59][60][62][63]. Second, the past experiments used high or nearly toxic doses of Se (0.9-4.5 mg/kg body weight) [29][30][31][32][33][34][35][36][37][38][39], while recent experiments used Se levels not exceeding their maximal tolerable limits (≤33.0 mg Se/kg diet).…”

“…Second, the past experiments used high or nearly toxic doses of Se (0.9-4.5 mg/kg body weight) [29][30][31][32][33][34][35][36][37][38][39], while recent experiments used Se levels not exceeding their maximal tolerable limits (≤33.0 mg Se/kg diet). Finally, many of the past animal studies lasted only 2 to 8 weeks, whereas in most of recent animal studies the duration of Se supplementation has been 12 weeks or longer [53,[57][58][59][60][62][63].…”