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  • Title: [Thiazolidinediones in type 2 diabetes. Role of peroxisome proliferator-activated receptor gamma (PPARgamma)].
    Author: Dubois M, Vantyghem MC, Schoonjans K, Pattou F.
    Journal: Ann Endocrinol (Paris); 2002 Dec; 63(6 Pt 1):511-23. PubMed ID: 12527853.
    Abstract:
    Thiazolidinediones (TZDs) form a new class of oral antidiabetic agents. They improve insulin sensitivity and reduce glycemia, lipidemia and insulinemia in patients with type 2 diabetes. Their mechanism is original, since they activate the nuclear receptor Peroxisome Proliferator-Activated Receptor gamma (PPARgamma), altering the expression of genes involved in glucose and lipid homeostasis. Stimulating PPARgamma improves insulin sensitivity via several mechanisms: 1) it raises the expression of GLUT4 glucose transporter; 2) it regulates release of adipocyte-derived signaling factors that affect insulin sensitivity in muscle, and 3) it contributes to a turn-over in adipose tissue, inducing the production of smaller, more insulin sensitive adipocytes. TZDs also affect free fatty acids (FFA) lipotoxicity on islets, improving pancreatic B-cell function. In addition, triglycerides and FFA levels are lowered by TZDs. Two TZDs, rosiglitazone and pioglitazone, have recently obtained the European commercial licence, but their use is restricted to the association with metformin or sulfonylureas. At the moment, they are indicated in type 2 diabetes but could be of interest in a broader array of diseases related to insulin resistance. As for side effects, rosiglitazone and pioglitazone may cause increased plasma volume, edema and dose-related weight gain. TZDs offer an attractive option in the treatment of type 2 diabetes, though it may be too soon to determine if they prevent vascular complications, as do other oral antidiabetic agents. An important issue for the future will be to assess the influence of weight gain in the long time.
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