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 β-cell
function but also critically regulates β-cell differentiation, β-cell proliferation
and β-cell survival. Dysregulated β-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 β-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 β-cell development will be reviewed. Finally, the therapeutic potential
for intervention with GLP1 receptor agonists during the neonatal period will be discussed.
Key words
Exendin-4 · Transcription · Neogenesis · Islet · PDX · Diabetes · Regeneration
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stoffers@mail.med.upenn.edu
