Open AccessWNK1 kinase is essential for insulin‐stimulated GLUT4 trafficking in skeletal muscle
Author(s) -
Kim JiHee,
Kim Hanul,
Hwang KyuHee,
Chang Jae Seung,
Park KyuSang,
Cha SeungKuy,
Kong In Deok
Publication year - 2018
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12528
Subject(s) - glut4 , skeletal muscle , insulin resistance , glucose transporter , insulin receptor , medicine , endocrinology , protein kinase b , insulin , glucose uptake , irs1 , microbiology and biotechnology , biology , phosphorylation
With‐no‐lysine 1 (WNK1) kinase is a substrate of the insulin receptor/Akt pathway. Impaired insulin signaling in skeletal muscle disturbs glucose transporter 4 (GLUT4) translocation associated with the onset of type 2 diabetes (T2D). WNK1 is highly expressed in skeletal muscle. However, it is currently unknown how insulin signaling targeting WNK1 regulates GLUT4 trafficking in skeletal muscle, and whether this regulation is perturbed in T2D. Hereby, we show that insulin phosphorylates WNK1 at its activating site via a phosphatidylinositol 3‐kinase‐dependent mechanism. WNK1 promotes the cell surface abundance of GLUT4 via regulating TBC1D4. Of note, we observed insulin resistance and decreased WNK1 phosphorylation in T2D db/db mice as compared to the control mice. These results provide a new perspective on WNK1 function in the pathogenesis of hyperglycemia in T2D.