GLP-1

Abstract

Glucagon Like Peptide-1; Glucagon Like Peptide 1; GLP1; Incretin hormone Historical BackgroundIn 1906, it was first identified that the pancreas could be stimulated by factors from the gut to aid in removal of nutrients, and porcine small intestinal extract was used to treat diabetic patients (Graaf et al. 2016). In 1928, it was demonstrated that injection of secretin extracted from the small intestinal mucosa displays a hypoglycemic effect that is mediated through the pancreas (Creutzfeldt 2005). In the 1960s, it was shown that orally administered glucose induces a much stronger insulin response than that induced by intravenously administered glucose, despite the similar resulting plasma glucose levelsthis was termed the "incretin effect" (Creutzfeldt 2005;Graaf et al. 2016). Gastric inhibitory peptide (GIP) was the first incretin hormone to be discovered in 1975, which is produced by K cells of the small intestine (Creutzfeldt 2005). It was then observed in 1981 that antibodies against GIP did not abolish the incretin effect, which led to the discovery of glucagon-like peptide-1 (GLP-1) in the translational products of mRNAs isolated from pancreatic islets of anglerfish (Shields 1981;Graaf et al. 2016). Subsequently, it was shown that hamster and human preproglucagon cDNAs encode GLP-1 and -2, but only GLP-1 possessed the incretin activity (Graaf et al. 2016).