TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression
© 2019, The Author(s). 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 describ...
| Main Authors: | , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2022
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| Online Access: | https://hdl.handle.net/1721.1/135883.2 |
| _version_ | 1811073016936792064 |
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| author | 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 |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT 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 |
| author_sort | Hwang, Jun-Ha |
| collection | MIT |
| description | © 2019, The Author(s). 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. |
| first_indexed | 2024-09-23T09:27:21Z |
| format | Article |
| id | mit-1721.1/135883.2 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:27:21Z |
| publishDate | 2022 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/135883.22022-07-15T13:14:26Z 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 Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Biology © 2019, The Author(s). 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. 2022-07-15T13:14:25Z 2021-10-27T20:29:47Z 2022-07-15T13:14:25Z 2019 2019-07-18T14:56:37Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135883.2 en 10.1038/S41467-019-08287-X Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/octet-stream Springer Science and Business Media LLC Nature |
| spellingShingle | 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 |
| title | TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression |
| title_full | TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression |
| title_fullStr | TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression |
| title_full_unstemmed | TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression |
| title_short | TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression |
| title_sort | taz couples hippo wnt signalling and insulin sensitivity through irs1 expression |
| url | https://hdl.handle.net/1721.1/135883.2 |
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