The Development of Beta-cell Mass: Recent Progress and Potential Role of GLP-1

Abstract

Over the last decade, remarkable strides in incretin hormone biology have laid the foundation for our more recent appreciation that GLP-1 not only regulates mature beta-cell function but also critically regulates beta-cell differentiation, beta-cell proliferation and beta-cell survival. Dysregulated beta-cell growth and function are central to the pathophysiology of both type 1 and type 2 diabetes. Thus, GLP-1 receptor agonists are being intensively developed for the treatment of human diabetes and are likely to become available to clinical use in the near future. A general overview of beta-cell development will be provided, with particular emphasis on recent contributions to our understanding of pancreas and islet development during the embryonic, fetal and neonatal periods. The transcriptional hierarchy and extracellular signals governing events during these periods will be highlighted. Evidence suggesting a role for endogenous GLP-1 and GLP-1 receptor during beta-cell development will be reviewed. Finally, the therapeutic potential for intervention with GLP1 receptor agonists during the neonatal period will be discussed.