PPAR-gamma agonists and their role in type 2 diabetes mellitus management

Type 2 diabetes mellitus and obesity are the most frequent endocrine-metabolic diseases in the world and their pathogenic basis are characterized by insulin resistance and insulin secretion defects that can be demonstrated through several alterations in carbohydrates, lipids, and protein metabolism. The peroxisome proliferator-activated receptors have been identified as key regulators of glucose and lipid metabolism, because they act as transcription factors that stimulate protein synthesis in a wide variety of processes (energetic metabolism, proliferation, and cellular differentiation), of which have been identified 3 types (alpha, beta/delta, gamma). The thiazolidenediones are compounds that act as agonists of the peroxisome proliferator-activated receptor-gamma increasing the tissues sensibility (muscle, adiposity tissue, and liver) to the insulin action; that is why they are used nowadays in treatment of type 2 diabetes mellitus. These drugs produce several of adverse effects, such as weight increased, edema, anemia, pulmonary edema, and congestive cardiac failure. Even their use have been related for some studies to an increased in the myocardium infarct risk; this correlation has not been a strong determinant to remove them from the market.