Targeting Mitochondrial Biogenesis to Treat Insulin Resistance

Author(s): Monica Zamora, Josep A. Villena.

Journal Name: Current Pharmaceutical Design

Volume 20 , Issue 35 , 2014

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Abstract:

Over the last century, the prevalence of type 2 diabetes has dramatically increased, reaching the status of epidemic. Because insulin resistance is considered the primary cause of type 2 diabetes, the identification of the cellular processes and gene networks that lead to an impairment of insulin action in target tissues is of crucial importance for the development of new drugs and therapeutic strategies to treat or prevent the disease. Numerous studies in humans and animal models have shown that insulin resistance is frequently associated to reduced mitochondrial mass or oxidative function in insulin sensitive tissues, leading to the hypothesis that defective overall mitochondrial activity could play a relevant role in the etiology of insulin resistance and, therefore, in type 2 diabetes. Although the causal relationship between mitochondrial dysfunction and insulin resistance is still controversial, numerous studies show that lifestyle or pharmacological interventions that improve insulin sensitivity are frequently associated to an increase in mitochondrial function and whole body energy expenditure. Therefore, increasing mitochondrial mass and oxidative activity is viewed as a potential therapeutic approach for the treatment of insulin resistance. Here, we review the current knowledge on the role of mitochondria in the pathogenesis of insulin resistance and discuss some of the potential therapeutic strategies and pharmacological targets for the treatment of insulin resistance based on the activation of mitochondrial biogenesis and the increase of mitochondrial oxidative function.

Keywords: Type 2 diabetes, mitochondrial dysfunction, calorie restriction, exercise, AMPK, SIRT1, PGC-1.

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Article Details

VOLUME: 20
ISSUE: 35
Year: 2014
Page: [5527 - 5557]
Pages: 31
DOI: 10.2174/1381612820666140306102514
Price: $58

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