Regulation of beta-cell mass by hormones and growth factors

Substantial new information has accumulated on molecular mechanisms of panc reas development, regulation of beta -cell gene expression, and the role of growth factors in the differentiation, growth, and regeneration of beta -c ells. The present review focuses on some recent studies on the mechanism of action of cytokines such as growth hormone (GH) and prolactin (PRL) in bet a -cell proliferation and gene expression-in particular, the role of signal transducers and activators of transcription (STAT) proteins. The implicati on of the discovery of suppressors of cytokine signaling (SOCS) proteins fo r the interaction between stimulatory and inhibitory cytokines, including G H, PRL, leptin, and the proinflammatory cytokines interleukin-1 and interfe ron-gamma, in beta -cell survival is not yet clear. Recent studies indicate a role of cell adhesion molecules and the delta-like protein preadipocyte factor 1/fetal antigen 1 (Pref-1/FA-l) in cytokine-induced beta -cell growt h and development. Surprisingly, glucagon-like peptide-1 (GLP-1) was recent ly found to stimulate not only insulin secretion but also beta -cell replic ation and differentiation, which may present a new perspective in treatment of type 2 diabetes. Together with the intriguing reports on positive effec ts of insulin on both beta -cell growth and function, a picture is emerging of an integrated network of signaling events acting in concert to control beta -cell mass adaptation to insulin demand.