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TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression

Title
TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression
Authors
Hwang J.-H.Kim A.R.Kim K.M.Il Park J.Oh H.T.Moon S.A.Byun M.R.Jeong H.Kim H.K.Yaffe M.B.Hwang E.S.Hong J.-H.
Ewha Authors
황은숙정하나
SCOPUS Author ID
황은숙scopus; 정하나scopus
Issue Date
2019
Journal Title
Nature Communications
ISSN
2041-1723JCR Link
Citation
Nature Communications vol. 10, no. 1
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Insulin regulates blood glucose levels by binding its receptor and stimulating downstream proteins through the insulin receptor substrate (IRS). Impaired insulin signalling leads to metabolic syndrome, but the regulation of this process is not well understood. Here, we describe a novel insulin signalling regulatory pathway involving TAZ. TAZ upregulates IRS1 and stimulates Akt- and Glut4-mediated glucose uptake in muscle cells. Muscle-specific TAZ-knockout mice shows significantly decreased Irs1 expression and insulin sensitivity. Furthermore, TAZ is required for Wnt signalling-induced Irs1 expression, as observed by decreased Irs1 expression and insulin sensitivity in muscle-specific APC- and TAZ-double-knockout mice. TAZ physically interacts with c-Jun and Tead4 to induce Irs1 transcription. Finally, statin administration decreases TAZ, IRS1 level and insulin sensitivity. However, in myoblasts, the statin-mediated decrease in insulin sensitivity is counteracted by the expression of a constitutively active TAZ mutant. These results suggest that TAZ is a novel insulin signalling activator that increases insulin sensitivity and couples Hippo/Wnt signalling and insulin sensitivity. © 2019, The Author(s).
DOI
10.1038/s41467-019-08287-x
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약학대학 > 약학과 > Journal papers
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