Redox regulation of insulin sensitivity due to enhanced fatty acid utilization in the mitochondria

Paul M. Rindler, Clair L. Crewe, Jolyn Fernandes, Michael Kinter, Luke I. Szweda

Research output: Contribution to journalReview article

31 Scopus citations

Abstract

Obesity enhances the risk for the development of type 2 diabetes and cardiovascular disease. Loss in insulin sensitivity and diminished ability of muscle to take up and use glucose are characteristics of type 2 diabetes. Paradoxically, regulatory mechanisms that promote utilization of fatty acids appear to initiate diet-induced insulin insensitivity. In this review, we discuss recent findings implicating increased mitochondrial production of the prooxidant H2O2 due to enhanced utilization of fatty acids, as a signal to diminish reliance on glucose and its metabolites for energy. In the short term, the ability to preferentially use fatty acids may be beneficial, promoting a metabolic shift that ensures use of available fat by skeletal muscle and heart while preventing intracellular glucose accumulation and toxicity. However, with prolonged consumption of high dietary fat and ensuing obesity, the near exclusive dependence on fatty acid oxidation for production of energy by the mitochondria drives insulin resistance, diabetes, and cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)H634-H643
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume305
Issue number5
DOIs
StatePublished - Sep 1 2013

Keywords

  • Insulin signaling
  • Metabolic flexibility
  • Mitochondria
  • Obesity
  • Redox signaling

ASJC Scopus subject areas

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

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