GLP-1 Effects on Islets: Hormonal, Neuronal, or Paracrine?

According to the classical incretin con-cept, glucagon-like peptide (GLP)-1is viewed as a hormone produced in the intestinal L cells and acting via the circulation on satiety in the brain, gut motility, and insulin and glucagon secretion in the pancreatic islet. How-ever, in contrast to typical hormones, plasma levels of GLP-1 are relatively low with a very short half-life. Furthermore, GLP-1 is rapidly inactivated by dipep-tidyl peptidase-4 (DPP-4) in the vicinity of L cells within,1 min from the secre-tion of the gut peptide (1,2). This rapid metabolism of GLP-1 raises questions about how its effects are mediated on target organs such as pancreatic b-cells.