Impaired mitochondrial oxidative phosphorylation in multiple insulin-sensitive tissues of humans with type 2 diabetes mellitus.

Alteration of mitochondrial oxidative phosphorylation (OXPHOS) may contribute to insulin resistance. It is unclear, however, which characteristics are common to insulin-sensitive tissues. Using an oligonucleotide microarray and quantitative real-time polymerase chain reaction, the gene expression profiles of skeletal muscle, visceral adipose tissue and liver from autopsy donors with and without type 2 diabetes mellitus were determined. Common dysregulated genes were enriched in mitochondrial OXPHOS, and most of these genes were down-regulated in both the skeletal muscle and visceral adipose tissue of diabetic subjects, but up-regulated in diabetic liver. Messenger RNA (mRNA) for peroxisome proliferator-activated receptor-gamma co-activator 1alpha was significantly increased in diabetic liver but significantly reduced in diabetic skeletal muscle. Tumour necrosis factor-alpha mRNA was significantly down-regulated in diabetic visceral adipose tissue. The mitochondrial DNA content was slightly, though not significantly, reduced in diabetic liver and diabetic skeletal muscle. It is concluded that defects in OXPHOS genes and individual transcription co-factors in insulin-sensitive tissues may play an important role in the development of type 2 diabetes and the insulin-resistant state.