Journal de cytologie et d'histologie

The Role of TGF-ß Signaling in ß-Cell Dysfunction and Type 2 Diabetes: A Review. J Cytol Histol 5:282.

Abstract

Shane Fischbach and George K. Gittes

Type 2 Diabetes (T2D) is a global epidemic that affects hundreds of millions of individuals. The pancreatic β-cell has long been the focus of studies pertaining to T2D, but the therapies that exist to date are inadequate. Devising new therapies will require a more detailed understanding of the pathogenesis of T2D and of the normal function of the β-cell. In particular, there is a great need to understand the signaling pathways that govern normal β-cell function and that become dysfunctional during the progression to diabetes. The Transforming Growth Factor β (TGF-β) signaling pathway is implicated in nearly all tissue types in the body, and has been shown to play a role in pancreas development and homeostasis, including β-cell regeneration after pancreatic insult. TGF-β exerts its cellular effects through transcriptional activity of downstream SMAD molecules, as well as through cross-talk with other signaling pathways. Accumulating evidence suggests that β-cell failure in T2D is a multifaceted process that may include islet inflammation, increased β-cell apoptosis, reduced β-cell proliferation, and/or β-cell dedifferentiation to a progenitorlike state. This review details the known roles of TGF-β signaling in dedifferentiation-induced and inflammationinduced β-cell failure, and draws on the apparent coordinated regulation of β-cell proliferation and the β-cell differentiation state to offer new hypotheses about β-cell failure in T2D.