Signalling to translation in pancreatic beta-cells
Prof. Terrence Herbert University of Leicester Sponsored by MOLECULAR DEVICES
The development of type 2 diabetes occurs when pancreatic -cells fail to compensate for insulin resistance in peripheral tissues due to defects in insulin secretion or loss of -cell mass. Importantly, both pancreatic beta cell function and mass can be modulated by nutrients and hormones, which are mediated, at least in part, by: 1. changes in the rate of protein synthesis and/or the activity of key components of the translational machinery and; 2. the activation of the unfolded protein response. This talk will focus on the molecular mechanisms by which glucose and hormones, such as glucagon like peptide-1 (GLP1), stimulate protein synthesis with particular focus on the role and regulation of mTOR and the ER transmembrane kinase PERK. Recent relevant publications: Gomez E, Powell ML, Bevington A, Herbert TP. A decrease in cellular energy status stimulates PERK-dependent eIF2alpha phosphorylation and regulates protein synthesis in pancreatic beta-cells. Biochem J. 2008 Mar 15;410(3):485-93. Herbert TP. PERK in the life and death of the pancreatic beta-cell. Biochem Soc Trans. 2007 Nov;35(Pt 5):1205-7. Review. Greenman IC, Gomez E, Moore CE, Herbert TP. Distinct glucose-dependent stress responses revealed by translational profiling in pancreatic beta-cells.J Endocrinol. 2007 Jan;192(1):179-87. Greenman IC, Gomez E, Moore CE, Herbert TP. The selective recruitment of mRNA to the ER and an increase in initiation are important for glucose-stimulated proinsulin synthesis in pancreatic beta-cells. Biochem J. 2005 Oct 15;391(Pt 2):291-300. Gomez E, Powell ML, Greenman IC, Herbert TP. Glucose-stimulated protein synthesis in pancreatic beta-cells parallels an increase in the availability of the translational ternary complex (eIF2-GTP.Met-tRNAi) and the dephosphorylation of eIF2 alpha. J Biol Chem. 2004 Dec 24;279(52):53937-46. Website address http://www.le.ac.uk/cpp/research/tph.html
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