Thiazolidinediones in prediabetes and early type 2 diabetes: What can be learned about that disease's pathogenesis

Several clinical trials have shown a high success rate of thiazolidinediones (TZDs) in prediabetes and early type 2 diabetes. The presumed mechanism of this effect has shifted from the best known effect of these agents to improve insulin sensitivity, to preservation of beta-cell function. The common explanation for this effect is unloading of the islet beta cell from the insulin resistance-induced hyperstimulation that eventually leads to beta-cell failure, so-called beta-cell rest. However, a recent finding is powerful biological effects of peroxisome proliferator-activated receptor (PPAR)gamma signaling in islet beta cells. This article reviews this topic by first describing the TZD intervention studies. Then it provides an overview of the current concepts regarding the beta-cell overwork and rest hypotheses, and the recent information about PPAR gamma signaling effects in beta cells.