Relationships between exercise, mitochondrial biogenesis and type 2 diabetes.

Abstract

Skeletal muscle is the major site of insulin-stimulated glucose utilization in the body. Central to this process is oxidative metabolism, which is controlled by mitochondria. Therefore, defects in the biogenesis of this organelle can impact the ability of muscle to oxidize substrates and can have grave consequences on the action of insulin on glucose uptake. In healthy muscle, glucose and free fatty acids (FFAs) are efficiently metabolized preventing the accumulation of harmful lipid by-products. In contrast, in pre-diabetic conditions, reduced oxidative capacity, high levels of reactive oxygen species, and chronic elevations in FFAs culminate in greater intramyocellular lipids and lipid metabolites that interfere with insulin signaling pathways, and contribute to lower insulin sensitivity. While the extent of the involvement of mitochondria in insulin resistance and type 2 diabetes (T2D) is still an ongoing debate, there is compelling evidence to suggest that dysfunction in mitochondria, mediated by changes in gene expression, morphology, and mitochondrial turnover, contributes to the dysregulation of insulin signaling pathways observed with this metabolic syndrome. In the present review, we discuss our current understanding of mitochondrial biogenesis and highlight how dysfunction in key mitochondrial biogenesis pathways may play an important role in the pathogenesis of T2D. Moreover, we provide evidence supporting the therapeutic value of exercise in the prevention and treatment of metabolic syndromes such as T2D.