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Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy
Some recent studies associated insulin therapy with negative cardiovascular events and shorter lifespan. SUR2A, a K(ATP) channel subunit, regulate cardioprotection and cardiac ageing. Here, we have tested whether glucose and insulin regulate expression of SUR2A/K(ATP) channel subunits and resistance...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132176/ https://www.ncbi.nlm.nih.gov/pubmed/30211323 http://dx.doi.org/10.1016/j.bbrep.2018.08.005 |
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author | Du, Qingyou Jovanović, Sofija Sukhodub, Andriy Ngoi, Yong Shi Lal, Aashray Zheleva, Marina Jovanović, Aleksandar |
author_facet | Du, Qingyou Jovanović, Sofija Sukhodub, Andriy Ngoi, Yong Shi Lal, Aashray Zheleva, Marina Jovanović, Aleksandar |
author_sort | Du, Qingyou |
collection | PubMed |
description | Some recent studies associated insulin therapy with negative cardiovascular events and shorter lifespan. SUR2A, a K(ATP) channel subunit, regulate cardioprotection and cardiac ageing. Here, we have tested whether glucose and insulin regulate expression of SUR2A/K(ATP) channel subunits and resistance to metabolic stress in heart H9c2 cells. Absence of glucose in culture media decreased SUR2A mRNA, while mRNAs of Kir6.2, Kir6.1, SUR1 and IES SUR2B were increased. 2-deoxyglucose (50 mM) decreased mRNAs of SUR2A, SUR2B and SUR1, did not affect IES SUR2A and IES SUR2B mRNAs and increased Kir6.2 mRNA. No glucose and 2-deoxyglucose (50 mM) decreased resistance to an inhibitor of oxidative phosphorylation, DNP (10 mM). 50 mM glucose did not alter K(ATP) channel subunits nor cellular resistance to DNP (10 mM). Insulin (20 ng/ml) in both physiological and high glucose (50 mM) down-regulated SUR2A while upregulating Kir6.1 and Kir6.2 (in high glucose only). Insulin (20 ng/ml) in physiological and high glucose decreased cell survival in DNP (10 mM). As opposed to Kir6.2, infection with SUR2A resulted in titre-dependent cytoprotection. We conclude that insulin decreases resistance to metabolic stress in H9c2 cells by decreasing SUR2A expression. Lower cardiac SUR2A levels underlie increased myocardial susceptibility to metabolic stress and shorter lifespan. |
format | Online Article Text |
id | pubmed-6132176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-61321762018-09-12 Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy Du, Qingyou Jovanović, Sofija Sukhodub, Andriy Ngoi, Yong Shi Lal, Aashray Zheleva, Marina Jovanović, Aleksandar Biochem Biophys Rep Research Article Some recent studies associated insulin therapy with negative cardiovascular events and shorter lifespan. SUR2A, a K(ATP) channel subunit, regulate cardioprotection and cardiac ageing. Here, we have tested whether glucose and insulin regulate expression of SUR2A/K(ATP) channel subunits and resistance to metabolic stress in heart H9c2 cells. Absence of glucose in culture media decreased SUR2A mRNA, while mRNAs of Kir6.2, Kir6.1, SUR1 and IES SUR2B were increased. 2-deoxyglucose (50 mM) decreased mRNAs of SUR2A, SUR2B and SUR1, did not affect IES SUR2A and IES SUR2B mRNAs and increased Kir6.2 mRNA. No glucose and 2-deoxyglucose (50 mM) decreased resistance to an inhibitor of oxidative phosphorylation, DNP (10 mM). 50 mM glucose did not alter K(ATP) channel subunits nor cellular resistance to DNP (10 mM). Insulin (20 ng/ml) in both physiological and high glucose (50 mM) down-regulated SUR2A while upregulating Kir6.1 and Kir6.2 (in high glucose only). Insulin (20 ng/ml) in physiological and high glucose decreased cell survival in DNP (10 mM). As opposed to Kir6.2, infection with SUR2A resulted in titre-dependent cytoprotection. We conclude that insulin decreases resistance to metabolic stress in H9c2 cells by decreasing SUR2A expression. Lower cardiac SUR2A levels underlie increased myocardial susceptibility to metabolic stress and shorter lifespan. Elsevier 2018-09-06 /pmc/articles/PMC6132176/ /pubmed/30211323 http://dx.doi.org/10.1016/j.bbrep.2018.08.005 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Du, Qingyou Jovanović, Sofija Sukhodub, Andriy Ngoi, Yong Shi Lal, Aashray Zheleva, Marina Jovanović, Aleksandar Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy |
title | Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy |
title_full | Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy |
title_fullStr | Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy |
title_full_unstemmed | Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy |
title_short | Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy |
title_sort | insulin down-regulates cardioprotective sur2a in the heart-derived h9c2 cells: a possible explanation for some adverse effects of insulin therapy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132176/ https://www.ncbi.nlm.nih.gov/pubmed/30211323 http://dx.doi.org/10.1016/j.bbrep.2018.08.005 |
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