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.
Highlights
Diabetes mellitus is a group of metabolic diseases characterised by hyperglycemia resulting from defects in insulin secretion, insulin action, or both [1]
Insulin is the main therapy for type 1 diabetes and it is sometimes used for therapy of type 2 diabetes [3]
In the present study we have shown that insulin decreases resistance to metabolic stress in heart embryonic H9c2 cells by decreasing expression of SUR2A
Summary
Diabetes mellitus is a group of metabolic diseases characterised by hyperglycemia resulting from defects in insulin secretion, insulin action, or both [1]. Insulin is a peptide hormone produced by pancreatic β-cells that regulates metabolism of carbohydrates and fats [2]. Some more recent studies reported that insulin have cardiac effects that would not be expected from a cardioprotective hormone. It has been demonstrated that insulin inhibits cardioprotection afforded by ischaemic preconditioning [9] while in patients with type 2 diabetes, concerns about negative cardiac events when insulin is used as a therapeutic have been raised [10]. A large meta-analysis suggested that insulin treatment is associated with a significantly higher short and long-term adverse cardiovascular outcomes after percutaneous coronary intervention compared to diabetic patients not treated by insulin therapy [11]
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