کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8258468 | 1534608 | 2018 | 39 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Herpud1 impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca2+-calcineurin-Akt axis
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کلمات کلیدی
AdLacZCainIP3Ro-Phenylenediamine - o-phenylenediamineSmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAopd - UPDAkt - آکتinsulin - انسولینCSA - ایالات مؤتلفهٔ آمریکاCyclosporine A - سیکلوسپورینAendoplasmic reticulum - شبکه آندوپلاسمی Skeletal muscle - عضله اسکلتیcalcineurin inhibitor - مهار کننده کالسینورینknockout - ناکاوتPropidium iodide - پروتئین یدیدCalcium - کلسیمCalcineurin - کلسینورینinsulin receptor - گیرنده انسولین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Skeletal muscle plays a central role in insulin-controlled glucose homeostasis. The molecular mechanisms related to insulin resistance in this tissue are incompletely understood. Herpud1 is an endoplasmic reticulum membrane protein that maintains intracellular Ca2+ homeostasis under stress conditions. It has recently been reported that Herpud1-knockout mice display intolerance to a glucose load without showing altered insulin secretion. The functions of Herpud1 in skeletal muscle also remain unknown. Based on these findings, we propose that Herpud1 is necessary for insulin-dependent glucose disposal in skeletal muscle. Here we show that Herpud1 silencing decreased insulin-dependent glucose uptake, GLUT4 translocation to the plasma membrane, and Akt Ser473 phosphorylation in cultured L6 myotubes. A decrease in insulin-induced Akt Ser473 phosphorylation was observed in soleus but not in extensor digitorum longus muscle samples from Herpud1-knockout mice. Herpud1 knockdown increased the IP3R-dependent cytosolic Ca2+ response and the activity of Ca2+-dependent serine/threonine phosphatase calcineurin in L6 cells. Calcineurin decreased insulin-dependent Akt phosphorylation and glucose uptake. Moreover, calcineurin inhibition restored the insulin response in Herpud1-depleted L6 cells. Based on these findings, we conclude that Herpud1 is necessary for adequate insulin-induced glucose uptake due to its role in Ca2+/calcineurin regulation in L6 myotubes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1864, Issue 5, Part A, May 2018, Pages 1653-1662
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1864, Issue 5, Part A, May 2018, Pages 1653-1662
نویسندگان
Mario Navarro-Marquez, Natalia Torrealba, Rodrigo Troncoso, Cesar Vásquez-Trincado, Marcelo Rodriguez, Pablo E. Morales, Elisa Villalobos, Yuka Eura, Lorena Garcia, Mario Chiong, Amira Klip, Enrique Jaimovich, Koichi Kokame, Sergio Lavandero,