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

Ji Hee Kim, Hanul Kim, Kyu Hee Hwang, Jae Seung Chang, Kyusang Park, Seungkuy Cha, Indeok Kong

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)1866-1874
Number of pages9
JournalFEBS Open Bio
Volume8
Issue number11
DOIs
Publication statusPublished - 2018 Nov 1

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Facilitative Glucose Transport Proteins
Medical problems
Type 2 Diabetes Mellitus
Muscle
Skeletal Muscle
Phosphotransferases
Insulin
Phosphatidylinositol 3-Kinase
Phosphorylation
Insulin Receptor
Hyperglycemia
Lysine
Insulin Resistance
Substrates

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kim, Ji Hee ; Kim, Hanul ; Hwang, Kyu Hee ; Chang, Jae Seung ; Park, Kyusang ; Cha, Seungkuy ; Kong, Indeok. / WNK1 kinase is essential for insulin-stimulated GLUT4 trafficking in skeletal muscle. In: FEBS Open Bio. 2018 ; Vol. 8, No. 11. pp. 1866-1874.
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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.",
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WNK1 kinase is essential for insulin-stimulated GLUT4 trafficking in skeletal muscle. / Kim, Ji Hee; Kim, Hanul; Hwang, Kyu Hee; Chang, Jae Seung; Park, Kyusang; Cha, Seungkuy; Kong, Indeok.

In: FEBS Open Bio, Vol. 8, No. 11, 01.11.2018, p. 1866-1874.

Research output: Contribution to journalArticle

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