한빛사 논문
Jun-Ha Hwang1, A Rum Kim1, Kyung Min Kim1, Jung Il Park1, Ho Taek Oh1, Sung A Moon1, Mi Ran Byun1, Hana Jeong2, Hyo Kyung Kim2, Michael B. Yaffe3, Eun Sook Hwang2,* & Jeong-Ho Hong1,*
1 Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea. 2 College of Pharmacy, Ewha Womans University, Seoul 03760, South Korea. 3 David H. Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
*Correspondence and requests for materials should be addressed to E.S.H. or to J.-H.H.
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.
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