Stress Response Signaling Pathways May Lead to Mitochondrial Biogenesis

  1. Mei-ling A. Joiner
  1. Department of Internal Medicine, University of Iowa, Iowa City, IA
  1. Corresponding author: Mei-ling A. Joiner, mei-ling-joiner{at}
  1. M.L. and M.-l.A.J. contributed equally to this article.

Diabetes, a worldwide epidemic, represents a major public health problem and the vast majority of the patients with diabetes presents with insulin resistance, a fundamental manifestation of this disease. Insulin resistance impairs glucose uptake into skeletal muscle, which takes up about 80% of postprandial glucose in healthy individuals (1). Thus, skeletal muscle plays an indispensable role in maintaining glucose homeostasis. However, the mechanisms underlying the development of insulin resistance remains poorly understood, which perhaps accounts for the lack of effective therapies.

Mitochondria, where low levels of superoxide radicals are constitutively generated as a by-product of electron transport, serve as the powerhouse and are also considered a main source for overproduction of reactive oxygen species (ROS) triggered by diabetes (2,3). Oxidative stress is a key pathological signal leading to diabetes complications (4,5). It has been disappointing that broad-spectrum antioxidant therapies have not been effective in improving outcomes in high-risk patients, including patients with diabetes (6), when used as primary prevention, suggesting that detailed knowledge of oxidative injury mechanisms is necessary to develop …

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