Endocrine Abstracts

The incretin hormone glucagon-like peptide-1 (GLP-1) has been proposed to increase beta cell mass, via effects on proliferation, apoptosis and neogenesis. However, the role of GLP-1 during normal human development is unclear. We have addressed this in human fetuses by quantifying GLP-1 secretion during fetal development and determining how GLP-1 signalling impacts on early human fetal pancreas in explant culture.

GLP-1 is first secreted by the stomach, duodenum, terminal ileum and rectum at 8 weeks post conception (wpc). Levels of GLP-1 increased considerably during fetal development, most notably within the terminal ileum (~60×) and rectum (~200×). Active GLP-1 was secreted by the fetal pancreas, with a significant increase in secretion from 12 wpc (~150×). By immunohistochemistry, GLP-1 co-localised with prohormone convertase 1/3, detected at low levels in fetal pancreatic alpha-cells as well as in enteroendocrine cells. Interestingly, the GLP-1 receptor (GLP-1R) was detected on PDX1-positive cells but absent on NEUROG3-positive cells and fetal beta cells. Culturing fetal pancreatic explants with long-acting GLP-1 analogue (Liraglutide) significantly increased the number of insulin-positive cells whilst decreasing proliferation of progenitors. No effect was observed on beta cell apoptosis.

Taken together, these studies identify for the first time active GLP-1 production from multiple sites within the developing human fetus including the pancreas, with the potential to impact on human pancreas development and beta cell differentiation.