Selenite and ebselen supplementation has been shown to possess anti-cataract potential in some experimental animal models of cataract, however, the underlying mechanisms remain unclear. The present study was designed to evaluate the anti-cataract effects and the underlying mechanisms of selenite and ebselen supplementation on galactose induced cataract in rats, a common animal model of sugar cataract. Transmission electron microscopy images of lens fiber cells (LFC) and lens epithelial cells (LEC) were observed in d-galactose-induced experimental cataractous rats treated with or without selenite and ebselen, also redox homeostasis and expression of proteins such as selenoprotein R (SELR), 15kD selenoprotein (SEP15), superoxide dismutase 1 (SOD1), catalase (CAT), β-crystallin protein, aldose reductase (AR) and glucose-regulated protein 78 (GRP78) were estimated in the lenses. The results showed that d-galactose injection injured rat lens and resulted in cataract formation; however, selenite and ebselen supplementation markedly alleviated ultrastructural injury of LFC and LEC. Moreover, selenite and ebselen supplementation could mitigate the oxidative damage in rat lens and increase the protein expressions of SELR, SEP15, SOD1, CAT and β-crystallin, as well as decrease the protein expressions of AR and GRP78. Taken together, these findings for the first time reveal the anti-cataract potential of selenite and ebselen in galactosemic cataract, and provide important new insights into the anti-cataract mechanisms of selenite and ebselen in sugar cataract.

•MAP improves hyperglycemia, hyperlipemia and vascular inflammation in diabetic mice.•MAP improves vascular and pancreatic oxidative stress in diabetic mice.•MAP causes increases in serum and pancreatic insulin contents in diabetic mice.•MAP improves hepatic gluconeogenesis and glycogen synthesis in diabetic mice.•MAP may be a potential therapeutic option for type 1 diabetes.The present study was designed to investigate the hypoglycemic activity and the potential mechanisms of Misgurnus anguillicaudatus polysaccharide (MAP) in streptozotocin-induced diabetic mice. MAP oral administration significantly decreased the blood levels of glucose, TC, TG, LDL-C, and increased the blood levels of HDL-C and insulin in diabetic mice, concurrent with increases in body weights and pancreatic insulin contents. Moreover, MAP reversed the increased mRNA expressions of PEPCK and the reduced glycogen contents in the liver of diabetic mice. Concurrently, MAP exhibited potent anti-inflammatory and anti-oxidative activities, as evidenced by the decreased blood levels of TNF-α, IL-6, monocyte chemoattractant protein-1, MDA, and also the elevated SOD and GPx activities in the serum of diabetic mice. Furthermore, MAP also significantly improved the blood markers of the impaired liver function and renal function in diabetic mice. Altogether, these results suggest that MAP may be a potential therapeutic option for type 1 diabetes.

•Selenite exacerbates hepatic insulin resistance in HFD/STZ-induced diabetic mice.•Selenite elevates hepatic gluconeogenesis and reduces glycolysis in diabetic mice.•Selenite exacerbates hepatic oxidative stress and triggers JNK signaling pathway.•Selenite elevates hepatic selenoprotein P expression in diabetic mice.Recent evidence suggests a potential pro-diabetic effect of selenite treatment in type 2 diabetics; however, the underlying mechanisms remain elusive. Here we investigated the effects and the underlying mechanisms of selenite treatment in a nongenetic mouse model of type 2 diabetes. High-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice were orally gavaged with selenite at 0.5 or 2.0 mg/kg body weight/day or vehicle for 4 weeks. High-dose selenite treatment significantly elevated fasting plasma insulin levels and insulin resistance index, in parallel with impaired glucose tolerance, insulin tolerance and pyruvate tolerance. High-dose selenite treatment also attenuated hepatic IRS1/Akt/FoxO1 signaling and pyruvate kinase gene expressions, but elevated the gene expressions of phosphoenolpyruvate carboxyl kinase (PEPCK), glucose 6-phosphatase (G6Pase), peroxisomal proliferator-activated receptor-γ coactivator 1α (PGC-1α) and selenoprotein P (SelP) in the liver. Furthermore, high-dose selenite treatment caused significant increases in MDA contents, protein carbonyl contents, and a decrease in GSH/GSSG ratio in the liver, concurrent with enhanced ASK1/MKK4/JNK signaling. Taken together, these findings suggest that high-dose selenite treatment exacerbates hepatic insulin resistance in mouse model of type 2 diabetes, at least in part through oxidative stress-mediated JNK pathway, providing new mechanistic insights into the pro-diabetic effect of selenite in type 2 diabetes.