title: The [pre-] history of the incretin concept.
abstract: The discoverers of secretin already thought of the existence of a chemical excitant for the internal secretion of the pancreas. Numerous experiments have been performed and published between 1906 and 1935 testing the effect of injected or ingested duodenal ("secretin") extracts on fasting or elevated blood glucose levels of normal or diabetic animals and humans with contradictory results. In 1940, after a series of negative dog experiments performed by an opinion leader, the existence of an incretin was considered questionable and further research stopped for more than 20 years. However, after the development of the radio-immunoassay, the incretin-concept has been revived in 1964, showing that significantly more insulin was released after ingestion of glucose than after intravenous injection. The possibility that nerves or one of the known gut hormones were responsible for the incretin effect could be ruled out. In 1970, glucose dependent insulinotropic polypeptide (GIP), and finally, in 1985 glucagon-like peptide 1 (GLP-1) and its truncated form GLP-1(7-36) were recognized as true incretins. Thereafter, multiple antidiabetic qualities and the therapeutic perspectives of GLP-1(7-36) and its analogues and mimetics have been demonstratred.
authors.affiliation: Department of Medicine, Georg-August-Universität, Göttingen, Germany. wcreutzfeldt@t-online.de
authors.forename: Werner
authors.initials: W
authors.lastname: Creutzfeldt
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy; D005749:Gastric Inhibitory Polypeptide / Q000266:history* / Q000627:therapeutic use; D019886:Gastrin-Releasing Peptide / Q000266:history / Q000627:therapeutic use; D005768:Gastrointestinal Hormones / Q000266:history / Q000627:therapeutic use; D005934:Glucagon / Q000266:history* / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007004:Hypoglycemic Agents / Q000266:history* / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D010446:Peptide Fragments / Q000266:history* / Q000627:therapeutic use; D010455:Peptides / Q000266:history / Q000494:pharmacology; D011498:Protein Precursors / Q000266:history* / Q000627:therapeutic use; D012633:Secretin / Q000627:therapeutic use
chemical_list: D005768:Gastrointestinal Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D012633:Secretin; D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D019886:Gastrin-Releasing Peptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C051322:glucagon-like peptide 1 (7-37)