Nuclear SMAD5 dances to a different tune in regulating insulin secretion.

In this issue of Cell Metabolism, Fang et al.1 report a novel pH-sensitive cellular signaling mechanism involving the transcription factor SMAD5 that regulates the vesicular secretion of insulin from pancreatic ß cells in response to dietary challenges. Dysregulation of this pathway may contribute to metabolic disorders such as type 2 diabetes mellitus.