TGF-β Signaling in Pancreatic Islet β Cell Development and Function

Pancreatic islet beta cells (beta-cells) synthesize and secrete insulin in response to rising glucose levels and thus are a prime target in both major forms of diabetes. Type 1 diabetes ensues due to autoimmune destruction of beta-cells. On the other hand, the prevailing insulin resistance and hyperglycemia in type 2 diabetes (T2D) elicits a compensatory response from beta-cells that involves increases in beta-cell mass and function. However, the sustained metabolic stress results in beta-cell failure, characterized by severe n-cell dysfunction and loss of p-cell mass. Dynamic changes to beta-cell mass also occur during pancreatic development that involves extensive growth and morphogenesis. These orchestrated events are triggered by multiple signaling pathways, including those representing the transforming growth factor beta (TGF-beta) superfamily.TGF-beta pathway ligands play important roles during endocrine pancreas development, beta-cell proliferation, differentiation, and apoptosis. Furthermore, new findings are suggestive ofTGF-beta's role in regulation of adult n-cell mass and function. Collectively, these findings support the therapeutic utility of targeting TGF-beta in diabetes. Summarizing the role of the various TGF-beta pathway ligands in beta-cell development, growth and function in normal physiology, and during diabetes pathogenesis is the topic of this mini-review.