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 β-cell function. The common explanation for this effect is unloading of the islet β cell from the insulin resistance-induced hyperstimulation that eventually leads to β-cell failure, so-called β-cell rest. However, a recent finding is powerful biological effects of peroxisome proliferator-activated receptor (PPAR)γ signaling in islet β cells. This article reviews this topic by first describing the TZD intervention studies. Then it provides an overview of the current concepts regarding the β-cell overwork and rest hypotheses, and the recent information about PPARγ signaling effects in β cells.