Pioglitazone is a thiazolidinedione that acts as an agonist at PPARα/γ receptors and also binds mitoNEET, a mitochondrial protein involved in energy homeostasis. Pioglitazone exhibits anti-diabetic, antacid, antidepressant, antinociceptive, and anti-diarrheal activities. In vivo, pioglitazone decreases levels of HDL, triglycerides, total cholesterol, insulin, blood glucose, and Hb1Ac. Pioglitazone may also have effects on angiogenesis, decreasing expression of HIF-1α and VEGF but increasing microvessel density in animal models of hind limb ischemia. This compound inhibits formation of ulcers in vivo potentially due to inhibition of IL-1β and iNOS and induction of cNOS. Additionally, pioglitazone decreases visceral hypersensitivity, suppresses defecation, and increases nociceptive thresholds in vivo.