STAT5 activity in pancreatic β-cells

Abstract

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.

Keywords::

• growth hormone
• pancreatic β-cell
• pregnancy
• prolactin
• signal transduction
• STAT5
• transcription factor
• Type 1 diabetes mellitus
• Type 2 diabetes mellitus

Financial & competing interests disclosure

We acknowledge support from the Danish Medical Research Council, the Danish Diabetes Association, the Novo Nordisk Foundation, Haensch Foundation, JDRF and the EU Integrated Project: BETACELLTHERAPY. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.