TGF-ß Signaling in Pancreatic Islet ß Cell Development and Function.

ABSTRACT

Pancreatic islet beta cells (ß-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 ß-cells. On the other hand, the prevailing insulin resistance and hyperglycemia in type 2 diabetes (T2D) elicits a compensatory response from ß-cells that involves increases in ß-cell mass and function. However, the sustained metabolic stress results in ß-cell failure, characterized by severe ß-cell dysfunction and loss of ß-cell mass. Dynamic changes to ß-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 ß (TGF-ß) superfamily. TGF-ß pathway ligands play important roles during endocrine pancreas development, ß-cell proliferation, differentiation, and apoptosis. Furthermore, new findings are suggestive of TGF-ß's role in regulation of adult ß-cell mass and function. Collectively, these findings support the therapeutic utility of targeting TGF-ß in diabetes. Summarizing the role of the various TGF-ß pathway ligands in ß-cell development, growth and function in normal physiology, and during diabetes pathogenesis is the topic of this mini-review.