کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5527330 1401577 2016 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
SIRT1-AMPK crosstalk is involved in high glucose-dependent impairment of insulin responsiveness in primary rat podocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
SIRT1-AMPK crosstalk is involved in high glucose-dependent impairment of insulin responsiveness in primary rat podocytes
چکیده انگلیسی


- SIRT1 protein level and activity decrease in insulin resistant podocytes.
- SIRT1 downregulation inhibits AMPK, but not Akt activity in podocytes.
- SIRT1 downregulation abolishes the effect of insulin on glucose uptake.
- Insulin-dependent increase of AMPK activity was suppressed in SIRT1-depleted cells.
- Treatments activating SIRT1 and AMPK may improve insulin resistance of podocytes.

Growing evidence indicates that in diabetes, high glucose concentrations affect podocyte metabolism and function. The crucial pathological feature of type 2 diabetes mellitus and metabolic syndrome is insulin resistance, often developed as a result of dysregulation of nutrient-responsible systems and disturbance of cellular homeostasis under diabetic conditions. Here, we report the involvement of the reciprocal interplay between deacetylase SIRT1 and protein kinase AMPK in podocyte high glucose-induced abolition of insulin-dependent glucose uptake, manifesting insulin resistance. Experiments were performed on primary rat podocytes cultured in standard or high glucose conditions. Immunodetection methods were used to determine SIRT1 protein level and AMPK phosphorylation degree. Insulin-stimulated changes in glucose uptake were used to determine podocyte responsiveness to insulin. SIRT1 activity was modulated by resveratrol, EX-527, or small interfering RNA targeting SIRT1. We have demonstrated that the absence of the stimulating effect of insulin on glucose uptake into primary rat podocytes after long-time exposition to high glucose concentrations, is a result of decreased SIRT1 protein levels and activity, associated with decreased AMPK phosphorylation degree, presumably underlying the induction of insulin resistance. Our findings suggest that the interplay between SIRT1 and AMPK is involved in the regulation of insulin action in podocytes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 349, Issue 2, 10 December 2016, Pages 328-338
نویسندگان
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