Authors: Dalgaard, Louise T; Billestrup, Nils; Nielsen, Jens H

Source: Expert Review of Endocrinology and Metabolism, Volume 3, Number 4, July 2008 , pp. 423-439(17)

Publisher: Expert Reviews

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

Document Type: Research article

DOI: http://dx.doi.org/10.1586/17446651.3.4.423

Affiliations: 1: Roskilde University, Department of Science, Universitetsvej 1, DK-4000 Roskilde, Denmark., Email: ltd@ruc.dk

Publication date: 2008-07-01

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• Expert Review of Endocrinology & Metabolism provides extensive coverage of state-of-the-art research and clinical advancements in the field of endocrine control and metabolism, with a focus on screening, prevention, diagnostics, existing and novel therapeutics, as well as related molecular genetics, pathophysiology and epidemiology
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