The discovery of glucagon-like peptide 1.
The discovery of glucagon-like peptide 1 (GLP-1) began more than two decades ago with the observations that anglerfish islet proglucagon messenger RNAs (mRNAs) contained coding sequences for two glucagon-related peptides arranged in tandem. Subsequent analyses revealed that mammalian proglucagon mRNAs encoded a precursor containing the sequence of pancreatic glucagon, intestinal glicentin and two glucagon-related peptides termed GLP-1 and GLP-2. Multidisciplinary approaches were then required to define the structure of biologically active GLP-1 7-36 amide and its role as an incretin, satiety hormone and, most recently, a neuroprotective peptide. This historial perspective outlines the use of traditional recombinant DNA approaches to derive the GLP-1 sequence and highlights the challenges and combination of clinical and basic science approaches required to define the physiology and pathophysiology of bioactive peptides discovered through genomics.
Lund
P Kay
PK
Department of Cell and Molecular Physiology, Nutrition and Center for Gastrointestinal, Biology and Disease, The University of North Carolina at Chapel Hill, North Carolina 27599-7545, USA. empk@med.unc.edu
D000818:Animals; D018076:DNA, Complementary / Q000378:metabolism; D005399:Fishes / Q000235:genetics; D005934:Glucagon / Q000235:genetics / Q000266:history* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D049673:History, 20th Century; D006728:Hormones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000266:history*; D052336:Proglucagon; D011498:Protein Precursors / Q000235:genetics / Q000266:history* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics
D018076:DNA, Complementary; D006728:Hormones; D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon