There is strong evidence of involvement of mitochondria in type 2 diabetes, causing or caused by insulin resistance of muscle, insulin secretion from the pancreas and in the complications of diabetes. Typically, the number and size of mitochondria is reduced in the muscle of diabetics, there is reduced mitochondrial biogenesis and switching of metabolic substrate use that is linked directly to mitochondrial enzymes. Insulin secretion from the pancreatic islet cells requires ATP and altered functioning of mitochondria and the resulting increased oxidative stress of these cells is thought to play a major part in the reduced insulin release.

Among the most convincing links between mitochondrial dysfunction and diabetes are the observed diabetic pathology of a point mutation in mtDNA encoding the tRNA for leucine, and the more recent finding that depletion of the mitochondrial nicotinamide nucleotide transhydrogenase (NNT) caused much reduced insulin secretion from islet cells.