Full metadata record
DC Field | Value | Language |
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dc.creator | Lopez-Pastor, A.R. (Andrea Raposo) | - |
dc.creator | Gomez-Hernandez, A. (Almudena) | - |
dc.creator | Diaz-Castroverde, S. (Sabela) | - |
dc.creator | González-Aseguinolaza, G. (Gloria) | - |
dc.creator | Gonzalez-Rodriguez, A. (Agueda) | - |
dc.creator | Castillo-García, G. (Gema) | - |
dc.creator | Fernandez, S. (Silvia) | - |
dc.creator | Escribano, O. (Oscar) | - |
dc.creator | Benito, M. (Manuel) | - |
dc.date.accessioned | 2022-03-22T08:03:16Z | - |
dc.date.available | 2022-03-22T08:03:16Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Lopez-Pastor, A.R. (Andrea Raposo); Gomez-Hernandez, A. (Almudena); Diaz-Castroverde, S. (Sabela); et al. "Liver-specific insulin receptor isoform A expression enhances hepatic glucose uptake and ameliorates liver steatosis in a mouse model of diet-induced obesity". Disease Models & Mechanisms. 12 (2), 2019, dmm036186 | es |
dc.identifier.issn | 1754-8403 | - |
dc.identifier.uri | https://hdl.handle.net/10171/63270 | - |
dc.description.abstract | Among the main complications associated with obesity are insulin resistance and altered glucose and lipid metabolism within the liver. It has previously been described that insulin receptor isoform A (IRA) favors glucose uptake and glycogen storage in hepatocytes compared with isoform B (IRB), improving glucose homeostasis in mice lacking liver insulin receptor. Thus, we hypothesized that IRA could also improve glucose and lipid metabolism in a mouse model of high-fatdiet-induced obesity. We addressed the role of insulin receptor isoforms in glucose and lipid metabolism in vivo. We expressed IRA or IRB specifically in the liver by using adeno-associated viruses (AAVs) in a mouse model of diet-induced insulin resistance and obesity. IRA, but not IRB, expression induced increased glucose uptake in the liver and muscle, improving insulin tolerance. Regarding lipid metabolism, we found that AAV-mediated IRA expression also ameliorated hepatic steatosis by decreasing the expression of Fasn, Pgc1a, Acaca and Dgat2 and increasing Scd-1 expression. Taken together, our results further unravel the role of insulin receptor isoforms in hepatic glucose and lipid metabolism in an insulin-resistant scenario. Our data strongly suggest that IRA is more efficient than IRB at favoring hepatic glucose uptake, improving insulin tolerance and ameliorating hepatic steatosis. Therefore, we conclude that a gene therapy approach for hepatic IRA expression could be a safe and promising tool for the regulation of hepatic glucose consumption and lipid metabolism, two key processes in the development of non-alcoholic fatty liver disease associated with obesity. | es_ES |
dc.description.sponsorship | This work was supported by Ministerio de Ciencia e Innovación (SAF2011/22555, SAF2014/51795-R and SAF2017-82133-R to M.B.), Instituto de Salud Carlos III (PIE14/00061 and CB07/08/0001 to M.B.) and Comunidad de Madrid (CT1/18-CT2/ 18/PEJD-2017-PRE/BMD-4111 to A.R.L.-P.). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | The Company of Biologists | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | Glucose metabolism | es_ES |
dc.subject | Insulin receptor isoforms | es_ES |
dc.subject | Adeno-associated viruses | es_ES |
dc.subject | Gene therapy | es_ES |
dc.subject | Non-alcoholic fatty liver disease | es_ES |
dc.subject | Insulin resistance | es_ES |
dc.title | Liver-specific insulin receptor isoform A expression enhances hepatic glucose uptake and ameliorates liver steatosis in a mouse model of diet-induced obesity | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.description.note | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. | es_ES |
dc.identifier.doi | 10.1242/dmm.036186 | - |
dadun.citation.number | 2 | es_ES |
dadun.citation.publicationName | Disease Models & Mechanisms | es_ES |
dadun.citation.startingPage | dmm036186 | es_ES |
dadun.citation.volume | 12 | es_ES |
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