Mitochondrial dysfunction has been implicated in both rare and common forms of type 2 diabetes (T2D) [1]–[4]. Individuals with T2D contain less mitochondria in their skeletal muscle [5], [6], and impaired mitochondrial function has been associated with T2D and insulin resistance, an intermediate phenotype and risk factor of diabetes [7]. In particular, oxidative phosphorylation (OXPHOS) activity in mitochondria, central for energy production in the cell, is reduced in certain populations of diabetic and insulin-resistant individuals [5], [8]. Furthermore, we found that the expression of OXPHOS genes is coordinately downregulated in diabetic versus healthy muscle [9], [10]. It has been proposed that decreased OXPHOS activity may contribute to T2D development by causing fatty acid accumulation in muscle cells, which in turn may inhibit insulin-stimulated glucose uptake [1], [2], [7], [8], [11], or by indirectly reducing glucose-stimulated insulin secretion from pancreatic ß-cells due to a decrease in ATP production [1]. However, it is still not clear whether the molecular and physiologic associations of mitochondria with diabetes are a cause or effect of the common form of T2D [1], [2], [12].
