The History of GLP-1 and the Debate Regarding Its Tissue-Specific Expression

Glucagon-like peptide-1 (GLP-1) is an incretin hormone encoded together with glucagon by the proglucagon gene. It has been widely accepted that GLP-1 and glucagon are derived from distinct post-translational processing of proglucagon in a tissue specific manner. GLP-1 is produced in intestinal L-cells where proglucagon is processed by prohormone convertase 1/3 (PC1/3), while glucagon is produced in pancreatic α-cells via PC2-mediated cleavage. Nonetheless, emerging evidence has now demonstrated GLP-1 is also produced in pancreatic islets, although its concentration is much lower than glucagon. Further studies have shown GLP-1 production and secretion can be up-regulated by various factors, in particular, hyperglycemia and β-cell damage. The importance of locally produced GLP-1 in pancreas for β-cell function has started to be recognized. Similar to circulating GLP-1, α- cell produced GLP-1 can promote insulin secretion, protect β-cells and enhance β-cell proliferation, thus is vital for β-cell function. This review focuses on these recent discoveries regarding GLP-1 production in pancreatic islets and its action within pancreatic tissue.