WNK1 kinase is essential for insulin-stimulated GLUT4 trafficking in skeletal muscle

Ji Hee Kim; Hanul Kim; Kyu Hee Hwang; Jae Seung Chang; Kyu Sang Park; Seung Kuy Cha; In Deok Kong

doi:10.1002/2211-5463.12528

WNK1 kinase is essential for insulin-stimulated GLUT4 trafficking in skeletal muscle

Ji Hee Kim, Hanul Kim, Kyu Hee Hwang, Jae Seung Chang, Kyu Sang Park, Seung Kuy Cha, In Deok Kong

Physiology

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1866-1874
Number of pages	9
Journal	FEBS Open Bio
Volume	8
Issue number	11
DOIs	https://doi.org/10.1002/2211-5463.12528
Publication status	Published - 2018 Nov

Bibliographical note

Funding Information:
We thank professors Chou-Long Huang (University of Iowa Carver College of Medicine) and Hyeon Soo Kim (Korea University, Korea) for providing materials. We also thank to Dr. Sohyun Kim and Eun-Ha Chang for proofreading. This study was supported by the Medical Research Center Program (2017R1A5A2015369) and the Basic Science Research Program (2015R1D1A1A01060454 and 2017R1D1 A3B03031760) through the National Research Foundation of Korea, and the Yonsei University Wonju Campus Future-Leading Research Initiative (2017-52-0082).

Funding Information:
We thank professors Chou-Long Huang (University of Iowa Carver College of Medicine) and Hyeon Soo Kim (Korea University, Korea) for providing materials. We also thank to Dr. Sohyun Kim and Eun-Ha Chang for proofreading. This study was supported by the Medical Research Center Program (2017R1A5A2015369) and the Basic Science Research Program (2015R1D1A1A01060454 and 2017R1D1A3B03031760) through the National Research Foundation of Korea, and the Yonsei University Wonju Campus Future-Leading Research Initiative (2017-52-0082).

Publisher Copyright:
© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)

UN SDGs

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title = "WNK1 kinase is essential for insulin-stimulated GLUT4 trafficking in skeletal muscle",

abstract = "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.",

author = "Kim, {Ji Hee} and Hanul Kim and Hwang, {Kyu Hee} and Chang, {Jae Seung} and Park, {Kyu Sang} and Cha, {Seung Kuy} and Kong, {In Deok}",

note = "Funding Information: We thank professors Chou-Long Huang (University of Iowa Carver College of Medicine) and Hyeon Soo Kim (Korea University, Korea) for providing materials. We also thank to Dr. Sohyun Kim and Eun-Ha Chang for proofreading. This study was supported by the Medical Research Center Program (2017R1A5A2015369) and the Basic Science Research Program (2015R1D1A1A01060454 and 2017R1D1 A3B03031760) through the National Research Foundation of Korea, and the Yonsei University Wonju Campus Future-Leading Research Initiative (2017-52-0082). Funding Information: We thank professors Chou-Long Huang (University of Iowa Carver College of Medicine) and Hyeon Soo Kim (Korea University, Korea) for providing materials. We also thank to Dr. Sohyun Kim and Eun-Ha Chang for proofreading. This study was supported by the Medical Research Center Program (2017R1A5A2015369) and the Basic Science Research Program (2015R1D1A1A01060454 and 2017R1D1A3B03031760) through the National Research Foundation of Korea, and the Yonsei University Wonju Campus Future-Leading Research Initiative (2017-52-0082). Publisher Copyright: {\textcopyright} 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.",

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AU - Cha, Seung Kuy

AU - Kong, In Deok

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N2 - 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.

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WNK1 kinase is essential for insulin-stimulated GLUT4 trafficking in skeletal muscle

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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