Mitochondrial Dysfunction in Obesity and Diabetes

US Endocrinology, 2010;6(1):20-27 DOI:


Mitochondrial abnormalities have been reported in both insulin-deficient and insulin-resistant states and in the related condition of obesity. The phrase ‘mitochondrial dysfunction’ is often used in this regard. However, beyond dysfunction, there is evidence for defects in mitochondrial biogenesis, number, morphology, and dynamics (fusion and fission). Diabetes and obesity are also associated with the overproduction of mitochondrial reactive oxygen species (ROS), leading to mitochondrial and cellular oxidative damage. This, in turn, contributes to the development and progression of diabetic complications and to worsening of the diabetic state per se. Here we will review the evidence for mitochondrial abnormalities in type 2 diabetes and obesity and consider underlying mechanisms. We will also discuss potential therapeutic interventions targeted at mitochondria.

Diabetes, obesity, mitochondria, superoxide, reactive oxygen species, respiration

Disclosure: The author has no conflicts of interest to declare.
Acknowledgements: The author is supported by Veterans Affairs medical research funds, grant NIH 1 R01 HL073166-01, and by funds donated by the Iowa Affiliate of the Fraternal Order of the Eagles.
Received: September 3, 2010 Accepted: November 4, 2010 Citation: US Endocrinology, 2010;6:20–7
Correspondence: William I Sivitz, MD, Professor, Department of Internal Medicine, Division of Endocrinology and Metabolism, The University of Iowa Hospitals and Clinics, 422GH, 200 Hawkins Drive, Iowa City, IA 52242. E:

The pathogenesis of type 2 diabetes includes pancreatic β-cell dysfunction and insulin resistance; most importantly in hepatocytes, myocytes, and adipocytes. Type 2 diabetes is well known to be a progressive disorder1 characterized by deteriorating capacity for insulin release and action. Both defects are recognizable early on and present even in non-diabetic offspring of patients with type 2 diabetes.2–4 However, there is general consensus that insulin sensitivity is impaired early, whereas worsening of hyperglycemia over time is related to β-cell dysfunction. Hence, insulin resistance in obesity is strongly associated with type 2 diabetes; the major reasons include fatty acid delivery to the liver (especially from intra-abdominal fat) and other organs and adipose tissue release of inflammatory cytokines and peptides that impair insulin signaling and islet insulin secretion. At cellular and molecular levels the pathogenesis of diabetes becomes far more complex. Here, the focus will be on the role of mitochondria and mitochondrial reactive oxygen species (ROS) in mediating the general mechanisms.

Mitochondrial Function by Cell Type
Our approach will be to consider mitochondrial function within the most relevant cell types including myocytes, hepatocytes, adipocytes, and islet β-cells as well as non-insulin-sensitive cells representing targets for complications. We will attempt to integrate defects in a way consistent with the pathophysiology of diabetes and its complications.
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