STAT5 activity in pancreatic β-cells.

Signal transducer and activator of transcription (STAT)5A and -5B are latent transcription factors activated by cytokines and hormones of the cytokine family. In pancreatic insulin-secreting β-cells, STAT5A and -5B are activated primarily by prolactin and growth hormone stimulation and are important mediators of the potent stimulation of proliferation and insulin production caused by these hormones. STAT5A and -5B are both expressed in β-cells and control the expression of a number of mRNAs implicated in cell replication control, insulin biosynthesis and secretion. In addition to STAT5A and -5B being transcriptional activators, they may also repress gene transcription. By these means, STAT5 proteins increase the levels of anti-apoptotic transcripts in β-cells and repress expression of pro-apoptotic genes. This review focuses on the anti-apoptotic role of STAT5 signaling, providing a mechanism for β-cell resistance to pro-apoptotic cytokines, Type 1 diabetes mellitus and obesity-associated β-cell stress. It is clear from studies of STAT5 signaling in pancreatic β-cells that STAT5 is important for postnatal β-cell compensatory growth (as in pregnancy or obesity) and in the defense against β-cell stress factors.