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

Jun Ha Hwang, A. Rum Kim, Kyung Min Kim, Jung Il Park, Ho Taek Oh, Sung A. Moon, Mi Ran Byun, Hana Jeong, Hyo Kyung Kim, Michael B. Yaffe, Eun Sook Hwang, Jeong-Ho Hong

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number421
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

Fingerprint

insulin
Insulin Resistance
Insulin
sensitivity
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Knockout Mice
knockout mice
Muscle
Insulin Receptor Substrate Proteins
Muscles
Myoblasts
muscles
glucose
Muscle Cells
Blood Glucose
Up-Regulation
muscle cells
Insulin Receptor
Glucose
Transcription

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression. / Hwang, Jun Ha; Kim, A. Rum; Kim, Kyung Min; Il Park, Jung; Oh, Ho Taek; Moon, Sung A.; Byun, Mi Ran; Jeong, Hana; Kim, Hyo Kyung; Yaffe, Michael B.; Hwang, Eun Sook; Hong, Jeong-Ho.

In: Nature Communications, Vol. 10, No. 1, 421, 01.12.2019.

Research output: Contribution to journalArticle

Hwang, JH, Kim, AR, Kim, KM, Il Park, J, Oh, HT, Moon, SA, Byun, MR, Jeong, H, Kim, HK, Yaffe, MB, Hwang, ES & Hong, J-H 2019, 'TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression', Nature Communications, vol. 10, no. 1, 421. https://doi.org/10.1038/s41467-019-08287-x
Hwang, Jun Ha ; Kim, A. Rum ; Kim, Kyung Min ; Il Park, Jung ; Oh, Ho Taek ; Moon, Sung A. ; Byun, Mi Ran ; Jeong, Hana ; Kim, Hyo Kyung ; Yaffe, Michael B. ; Hwang, Eun Sook ; Hong, Jeong-Ho. / TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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