کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2568274 1128431 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Selenite exacerbates hepatic insulin resistance in mouse model of type 2 diabetes through oxidative stress-mediated JNK pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Selenite exacerbates hepatic insulin resistance in mouse model of type 2 diabetes through oxidative stress-mediated JNK pathway
چکیده انگلیسی


• 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 289, Issue 3, 15 December 2015, Pages 409–418
نویسندگان
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