Restoring redox balance enhances contractility in heart trabeculae from type 2 diabetic rats exposed to high glucose

Niraj M. Bhatt, Miguel A. Aon, Carlo G. Tocchetti, Xiaoxu Shen, Swati Dey, Genaro Ramirez-Correa, Brianó Rourke, Wei Dong Gao, Sonia Cortassa

Research output: Contribution to journalArticlepeer-review

Abstract

Hearts from type 2 diabetic (T2DM) subjects are chronically subjected to hyperglycemia and hyperlipidemia, both thought to contribute to oxidizing conditions and contractile dysfunction. How redox alterations and contractility interrelate, ultimately diminishing T2DM heart function, remains poorly understood. Herein we tested whether the fatty acid palmitate (Palm), in addition to its energetic contribution, rescues function by improving redox [glutathione (GSH), NAD(P)H, less oxidative stress] in T2DM rat heart trabeculae subjected to high glucose. Using cardiac trabeculae from Zucker Diabetic Fatty (ZDF) rats, we assessed the impact of low glucose (EG) and high glucose (HG), in absence or presence of Palm or insulin, on force development, energetics, and redox responses. We found that in EG ZDF and lean trabeculae displayed similar contractile work, yield of contractile work (Ycw), representing the ratio of force time integral over rate of O2 consumption. Conversely, HG had a negative impact on Ycw, whereas Palm, but not insulin, completely prevented contractile loss. This effect was associated with higher GSH, less oxidative stress, and augmented matrix GSH/thioredoxin (Trx) in ZDF mitochondria. Restoration of myocardial redox with GSH ethyl ester also rescued ZDF contractile function in HG, independently from Palm. These results support the idea that maintained redox balance, via increased GSH and Trx antioxidant activities to resist oxidative stress, is an essential protective response of the diabetic heart to keep contractile function.

Original languageEnglish (US)
Pages (from-to)H291-H302
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume308
Issue number4
DOIs
StatePublished - 2015

Keywords

  • Antioxidant systems
  • Contractile work
  • Mitochondrial ros emission
  • Oxidative phosphorylation
  • Rate of respiration
  • Redox environment
  • Zucker diabetic fatty rat

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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