| First Author | Navarro-Marquez M | Year | 2018 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1864 |
| Issue | 5 Pt A | Pages | 1653-1662 |
| PubMed ID | 29486284 | Mgi Jnum | J:319285 |
| Mgi Id | MGI:6863519 | Doi | 10.1016/j.bbadis.2018.02.018 |
| Citation | Navarro-Marquez M, et al. (2018) Herpud1 impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca(2+)-calcineurin-Akt axis. Biochim Biophys Acta Mol Basis Dis 1864(5 Pt A):1653-1662 |
| abstractText | 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 Ca(2+) 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 Ser(473) phosphorylation in cultured L6 myotubes. A decrease in insulin-induced Akt Ser(473) phosphorylation was observed in soleus but not in extensor digitorum longus muscle samples from Herpud1-knockout mice. Herpud1 knockdown increased the IP3R-dependent cytosolic Ca(2+) response and the activity of Ca(2+)-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 Ca(2+)/calcineurin regulation in L6 myotubes. |
