Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy

Qingyou Du, Sofija Jovanović, Andriy Sukhodub, Yong Shi Ngoi, Aashray Lal, Marina Zheleva, Aleksandar Jovanović (Lead / Corresponding author)

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Abstract

Some recent studies associated insulin therapy with negative cardiovascular events and shorter lifespan. SUR2A, a KATP channel subunit, regulate cardioprotection and cardiac ageing. Here, we have tested whether glucose and insulin regulate expression of SUR2A/KATP 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 KATP 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.

Original languageEnglish
Pages (from-to)12-18
Number of pages7
JournalBiochemistry and Biophysics Reports
Volume16
Early online date6 Sep 2018
DOIs
Publication statusPublished - Dec 2018

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Down-Regulation
Insulin
Glucose
KATP Channels
Physiological Stress
Messenger RNA
Deoxyglucose
Therapeutics
Cytoprotection
Oxidative Phosphorylation
Culture Media
Insulin Resistance
Cell Survival
Aging of materials
Cells
Infection

Keywords

  • Glucose
  • Heart
  • Insulin
  • SUR2A

Cite this

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. In: Biochemistry and Biophysics Reports. 2018 ; Vol. 16. pp. 12-18.
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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. / Du, Qingyou; Jovanović, Sofija; Sukhodub, Andriy; Ngoi, Yong Shi; Lal, Aashray; Zheleva, Marina; Jovanović, Aleksandar (Lead / Corresponding author).

In: Biochemistry and Biophysics Reports, Vol. 16, 12.2018, p. 12-18.

Research output: Contribution to journalArticle

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T2 - A possible explanation for some adverse effects of insulin therapy

AU - Du, Qingyou

AU - Jovanović, Sofija

AU - Sukhodub, Andriy

AU - Ngoi, Yong Shi

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AU - Jovanović, Aleksandar

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