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 | |
| Publication status | Published - 2018 Nov |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
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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, Kyu Sang; Cha, Seung Kuy; Kong, In Deok.
In: FEBS Open Bio, Vol. 8, No. 11, 11.2018, p. 1866-1874.Research output: Contribution to journal › Article
TY - JOUR
T1 - WNK1 kinase is essential for insulin-stimulated GLUT4 trafficking in skeletal muscle
AU - Kim, Ji Hee
AU - Kim, Hanul
AU - Hwang, Kyu Hee
AU - Chang, Jae Seung
AU - Park, Kyu Sang
AU - Cha, Seung Kuy
AU - Kong, In Deok
PY - 2018/11
Y1 - 2018/11
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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85054505209&partnerID=8YFLogxK
U2 - 10.1002/2211-5463.12528
DO - 10.1002/2211-5463.12528
M3 - Article
AN - SCOPUS:85054505209
VL - 8
SP - 1866
EP - 1874
JO - FEBS Open Bio
JF - FEBS Open Bio
SN - 2211-5463
IS - 11
ER -