PGC-1α activation: a therapeutic target for type 2 diabetes?

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) has gained popularity as a very attractive target for diabetic therapies due to its role in lipid and glucose metabolism. Pharmacological activation of PGC-1α is thought to elicit health benefits. However, this notion has been questioned by increasing evidence, which suggests that insulin resistant is exacerbated when PGC-1α expression is far beyond normal physiological limits and is prevented under the condition of PGC-1α deficiency. This narrative review suggests that PGC-1α, as a master metabolic regulator, exerts roles in insulin sensitivity in a tissue-specific manner and in a physical activity/age-dependent fashion. When using PGC-1α as a target for therapeutic strategies against insulin resistance and T2DM, we should take these factors into consideration.Level of evidence: Level V, narrative review.