EHD2 regulates plasma membrane integrity and downstream insulin receptor signalling events
(2023) In Molecular Biology of the Cell 34(12).- Abstract
Adipocyte dysfunction is a crucial driver of insulin resistance and type 2 diabetes. We identified EH domain-containing protein 2 (EHD2) as one of the most highly upregulated genes at the early stage of adipose tissue expansion. EHD2 is a dynamin-related ATPase influencing several cellular processes, including membrane recycling, caveolae dynamics and lipid metabolism. Here, we investigated the role of EHD2 in adipocyte insulin signalling and glucose transport. Using C57BL6/N EHD2 knockout mice under short-term high-fat diet conditions and 3T3-L1 adipocytes we demonstrate that EHD2 deficiency is associated with deterioration of insulin signal transduction and impaired insulin-stimulated GLUT4 translocation. Furthermore, we show that... (More)
Adipocyte dysfunction is a crucial driver of insulin resistance and type 2 diabetes. We identified EH domain-containing protein 2 (EHD2) as one of the most highly upregulated genes at the early stage of adipose tissue expansion. EHD2 is a dynamin-related ATPase influencing several cellular processes, including membrane recycling, caveolae dynamics and lipid metabolism. Here, we investigated the role of EHD2 in adipocyte insulin signalling and glucose transport. Using C57BL6/N EHD2 knockout mice under short-term high-fat diet conditions and 3T3-L1 adipocytes we demonstrate that EHD2 deficiency is associated with deterioration of insulin signal transduction and impaired insulin-stimulated GLUT4 translocation. Furthermore, we show that lack of EHD2 is linked with altered plasma membrane lipid and protein composition, reduced insulin receptor expression, and diminished insulin-dependent SNARE protein complex formation. In conclusion, these data highlight the importance of EHD2 for the integrity of the plasma membrane milieu, insulin receptor stability, and downstream insulin receptor signalling events, involved in glucose uptake and ultimately underscore its role in insulin resistance and obesity.
(Less)
- author
- organization
- publishing date
- 2023-09-13
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Biology of the Cell
- volume
- 34
- issue
- 12
- article number
- ar124
- publisher
- American Society for Cell Biology
- external identifiers
-
- pmid:37703099
- scopus:85175742345
- ISSN
- 1939-4586
- DOI
- 10.1091/mbc.E23-03-0078
- language
- English
- LU publication?
- yes
- id
- b25bb3b1-00bc-4587-b6fb-d74d99ffd2ce
- date added to LUP
- 2023-10-25 21:34:36
- date last changed
- 2024-07-13 23:23:37
@article{b25bb3b1-00bc-4587-b6fb-d74d99ffd2ce, abstract = {{<p>Adipocyte dysfunction is a crucial driver of insulin resistance and type 2 diabetes. We identified EH domain-containing protein 2 (EHD2) as one of the most highly upregulated genes at the early stage of adipose tissue expansion. EHD2 is a dynamin-related ATPase influencing several cellular processes, including membrane recycling, caveolae dynamics and lipid metabolism. Here, we investigated the role of EHD2 in adipocyte insulin signalling and glucose transport. Using C57BL6/N EHD2 knockout mice under short-term high-fat diet conditions and 3T3-L1 adipocytes we demonstrate that EHD2 deficiency is associated with deterioration of insulin signal transduction and impaired insulin-stimulated GLUT4 translocation. Furthermore, we show that lack of EHD2 is linked with altered plasma membrane lipid and protein composition, reduced insulin receptor expression, and diminished insulin-dependent SNARE protein complex formation. In conclusion, these data highlight the importance of EHD2 for the integrity of the plasma membrane milieu, insulin receptor stability, and downstream insulin receptor signalling events, involved in glucose uptake and ultimately underscore its role in insulin resistance and obesity.</p>}}, author = {{Neuhaus, Mathis and Fryklund, Claes and Taylor, Holly and Borreguero-Muñoz, Andrea and Kopietz, Franziska and Ardalani, Hamidreza and Rogova, Oksana and Stirrat, Laura and Bremner, Shaun K and Spégel, Peter and Bryant, Nia J and Gould, Gwyn W and Stenkula, Karin G}}, issn = {{1939-4586}}, language = {{eng}}, month = {{09}}, number = {{12}}, publisher = {{American Society for Cell Biology}}, series = {{Molecular Biology of the Cell}}, title = {{EHD2 regulates plasma membrane integrity and downstream insulin receptor signalling events}}, url = {{http://dx.doi.org/10.1091/mbc.E23-03-0078}}, doi = {{10.1091/mbc.E23-03-0078}}, volume = {{34}}, year = {{2023}}, }