A Smad Signaling Network Regulates Islet Cell Proliferation

Pancreatic b-cell loss and dysfunction are critical components of all types of diabetes. Human and rodent b-cells are able to proliferate, and this proliferation is an important defense against the evolution and progression of diabetes. Transforming growth factor-b (TGF-b) signaling has been shown to affect b-cell development, proliferation, and function, but b-cell proliferation is thought to be the only source of new b-cells in the adult. Recently, b-cell dedifferentiation has been shown to be an important contributory mechanism to b-cell failure. In this study, we tie together these two pathways by showing that a network of intracellular TGF-b regulators, smads 7, 2, and 3, control b-cell proliferation after b-cell loss, and specifically