Herpud1 impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca2+ -calcineurin-Akt axis

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Mario Navarro-MarquezSergio Lavandero

Abstract

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 restore...Continue Reading

Citations

Sep 14, 2018·Microbiology and Immunology·Mie KurosawaYutaka Terao
Oct 19, 2019·Aging Cell·Fabiola Marín-AguilarMario D Cordero
Oct 12, 2019·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Fabiola Marín-AguilarMario D Cordero
Aug 30, 2020·International Journal of Molecular Sciences·Yuka EuraKoichi Kokame
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Shanshan YangZhiguang Su

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