کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5506671 | 1400301 | 2016 | 23 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Simvastatin induces insulin resistance in L6 skeletal muscle myotubes by suppressing insulin signaling, GLUT4 expression and GSK-3β phosphorylation
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کلمات کلیدی
PI3KFPPGSK-3βL6 myotubes3-hydroxy-3-methyl-glutaryl-coenzyme AHMG-CoAFTiGLUT4GGPPIRS1GGTIGlucose uptake - جذب گلوکزglucose transporter 4 - حمل کننده گلوکز 4insulin receptor substrate 1 - زیر بغل گیرنده انسولین 1Simvastatin - سیمواستاتینfarnesyl pyrophosphate - فارسیل پیرو فسفاتphosphoinositide 3-kinase - فسفینوزیتید 3-کینازfarnesyltransferase inhibitor - مهار کننده فارنزیل ترانسفرازgeranylgeranyl pyrophosphate - ژرینیل گرانیل پیرو فسفاتglycogen synthase kinase 3 beta - گلیکوزین سنتاز کیناز 3 بتاinsulin receptor - گیرنده انسولین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Simvastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor widely used for the treatment of hypercholesterolemia. Recent data indicates that simvastatin increases the risk of new-onset diabetes by impairing both insulin secretion and insulin sensitivity. However, systematic evaluation of mechanistic pathways is lacking. We aimed to explore the effects of simvastatin on glucose uptake and underlying mechanisms using L6 skeletal muscle myotubes. We performed our experiments at basal and insulin-stimulated conditions, at normal (5.5 mM) and high (16.7 mM) glucose. We showed that simvastatin inhibited glucose uptake at all conditions. We also found out that pravastatin, another widely used statin with different physicochemical properties, did not inhibit glucose uptake. The effect of simvastatin was reversed with geranylgeranyl pyrophosphate but not with farnesyl pyrophosphate, implying that reduced protein geranylgeranylation has a role in simvastatin-induced insulin resistance. Simvastatin also decreased phosphorylation of insulin receptor (IR), insulin receptor substrate 1 (IRS-1), AKT and glycogen synthase kinase 3β (GSK-3β), and downregulated GLUT4. In conclusion, our data indicate that simvastatin decreased both basal and insulin-stimulated glucose uptake through inhibiting the critical steps in IR/IRS-1/AKT signaling cascade, and by hindering GLUT4 function and normal regulation of glycogen synthesis, contributing to insulin resistance.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 480, Issue 2, 11 November 2016, Pages 194-200
Journal: Biochemical and Biophysical Research Communications - Volume 480, Issue 2, 11 November 2016, Pages 194-200
نویسندگان
Nagendra Yaluri, Shalem Modi, Tarja Kokkola,