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Glucagon-like peptide-1: difference between revisions

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10GLP-1 is generated by tissue-specific post-translational processing of [[Proglucagon|proglucagon]], the same precursor that yields [[glucagon]] in pancreatic alpha cells. In the intestine, prohormone convertase 1/3 liberates GLP-1 (7–37) and its C-terminally amidated form GLP-1 (7–36) amide, the latter accounting for the majority of circulating immunoreactive GLP-1 in humans.{{r|baggio2007}}10GLP-1 is generated by tissue-specific post-translational processing of [[Proglucagon|proglucagon]], the same precursor that yields [[glucagon]] in pancreatic alpha cells. In the intestine, prohormone convertase 1/3 liberates GLP-1 (7–37) and its C-terminally amidated form GLP-1 (7–36) amide, the latter accounting for the majority of circulating immunoreactive GLP-1 in humans.{{r|baggio2007}}
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+12Its principal actions are glucose-dependent potentiation of [[Insulin secretion|insulin secretion]], suppression of [[glucagon]] release, deceleration of [[Gastric emptying|gastric emptying]] and reduction of food intake through central [[Satiety signalling|satiety pathways]].{{r|holst2007,drucker2018}} Because the native hormone is inactivated within minutes by [[Dipeptidyl peptidase-4|dipeptidyl peptidase-4]], therapeutic exploitation of the pathway has depended on engineered analogues with extended half-lives — the [[GLP-1 receptor agonist|GLP-1 receptor agonists]] — rather than on the hormone itself.{{r|nauck2018}}
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12== Discovery and nomenclature ==14== Discovery and nomenclature ==
13The existence of a gut-derived insulin secretagogue was inferred long before any such molecule was isolated: oral glucose was observed to provoke a substantially larger insulin response than an intravenous glucose load producing the same glycaemic excursion, a difference termed the [[Incretin effect|incretin effect]].{{r|nauck1986}}15The existence of a gut-derived insulin secretagogue was inferred long before any such molecule was isolated: oral glucose was observed to provoke a substantially larger insulin response than an intravenous glucose load producing the same glycaemic excursion, a difference termed the [[Incretin effect|incretin effect]].{{r|nauck1986}}
26<ref name="holst2007">Holst JJ. "The physiology of glucagon-like peptide 1." ''Physiological Reviews'' 87(4):1409–1439 (2007). DOI:10.1152/physrev.00034.2006. PMID 17928588.</ref>28<ref name="holst2007">Holst JJ. "The physiology of glucagon-like peptide 1." ''Physiological Reviews'' 87(4):1409–1439 (2007). DOI:10.1152/physrev.00034.2006. PMID 17928588.</ref>
27<ref name="baggio2007">Baggio LL, Drucker DJ. "Biology of incretins: GLP-1 and GIP." ''Gastroenterology'' 132(6):2131–2157 (2007). DOI:10.1053/j.gastro.2007.03.054. PMID 17498508.</ref>29<ref name="baggio2007">Baggio LL, Drucker DJ. "Biology of incretins: GLP-1 and GIP." ''Gastroenterology'' 132(6):2131–2157 (2007). DOI:10.1053/j.gastro.2007.03.054. PMID 17498508.</ref>
+30<ref name="drucker2018">Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." ''Cell Metabolism'' 27(4):740–756 (2018). DOI:10.1016/j.cmet.2018.03.001. PMID 29617641.</ref>
+31<ref name="nauck2018">Nauck MA, Meier JJ. "Incretin hormones: their role in health and disease." ''Diabetes, Obesity and Metabolism'' 20(Suppl 1):5–21 (2018). DOI:10.1111/dom.13129. PMID 29364588.</ref>
28<ref name="nauck1986">Nauck M, Stöckmann F, Ebert R, Creutzfeldt W. "Reduced incretin effect in type 2 (non-insulin-dependent) diabetes." ''Diabetologia'' 29(1):46–52 (1986). PMID 3514343.</ref>32<ref name="nauck1986">Nauck M, Stöckmann F, Ebert R, Creutzfeldt W. "Reduced incretin effect in type 2 (non-insulin-dependent) diabetes." ''Diabetologia'' 29(1):46–52 (1986). PMID 3514343.</ref>
29<ref name="holst1987">Holst JJ, Ørskov C, Nielsen OV, Schwartz TW. "Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut." ''FEBS Letters'' 211(2):169–174 (1987). PMID 3542566.</ref>33<ref name="holst1987">Holst JJ, Ørskov C, Nielsen OV, Schwartz TW. "Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut." ''FEBS Letters'' 211(2):169–174 (1987). PMID 3542566.</ref>