کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5589628 | 1569809 | 2017 | 35 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
MicroRNA-21 regulates hepatic glucose metabolism by targeting FOXO1
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کلمات کلیدی
NAFLDPTTFOXO1Microrna-21GTTHFDinsulin tolerance test - آزمون تحمل انسولینpyruvate tolerance test - آزمون تحمل پیرواتITT - اینجاmiR-21 - به miR-21Nonalcoholic fatty liver disease - بیماری کبدی چربی غیر الکلیGlucose tolerance - تحمل گلوکزtriglyceride - تریگلیسریدglucose tolerance test - تست تحمل گلوکزInsulin sensitivity - حساسیت به انسولینhigh-fat diet - رژیم غذایی با چربی بالاGluconeogenesis - گلوکونوژنز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
ژنتیک
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Abnormal activation of hepatic gluconeogenesis is a major contributor to fasting hyperglycemia in type 2 diabetes; however, the potential role of microRNAs in gluconeogenesis remains unclear. Here, we showed that hepatic expression levels of microRNA-21 (miR-21) were decreased in db/db and high-fat diet (HFD)-induced diabetic mice. Adenovirus-mediated overexpression of miR-21 decreased the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and inhibited glucose production in primary mouse hepatocytes. Silencing of miR-21 reversed this effect. Overexpression of miR-21 in the livers of db/db and HFD-induced mice was able to suppress hepatic gluconeogenesis, subsequently decreasing blood glucose levels and improving glucose and insulin intolerance. Furthermore, overexpression of miR-21 in primary mouse hepatocytes and mouse livers decreased the protein levels of FOXO1 and increased hepatic insulin sensitivity. By contrast, silencing of miR-21 increased the protein levels of FOXO1, subsequently leading to a decrease in insulin sensitivity and impaired glucose intolerance in C57BL/6 mice fed with high-fat diet for 4Â weeks. Finally, we confirmed that FOXO1 was a potential target of miR-21. These results suggest that miR-21 is a critical regulator in hepatic gluconeogenesis and may provide a novel therapeutic target for treating insulin resistance and type 2 diabetes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gene - Volume 627, 5 September 2017, Pages 194-201
Journal: Gene - Volume 627, 5 September 2017, Pages 194-201
نویسندگان
Ailing Luo, Haibo Yan, Jichao Liang, Chunyuan Du, Xuemei Zhao, Lijuan Sun, Yong Chen,