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.