GLP-1 receptor: difference between revisions
Diff·revision 5 → 6·19:30, 4 Aug 2024
Difference between revision 5 and revision 6 of GLP-1 receptor. 2 lines changed; the page grew by 350 bytes.
| Revision 5 — 03:15, 22 Jul 2024 SafetySignalSid (talk) expand §Genetic variation 3,125 bytes ±0 | Revision 6 — 19:30, 4 Aug 2024 ReaderRosalie (talk) de-duplicate a repeated sentence 3,475 bytes +350 | ||
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| 10 | Activation couples principally to G<sub>s</sub>, raising intracellular cAMP and activating protein kinase A and the exchange protein Epac2. In the pancreatic beta cell this cascade amplifies, but does not initiate, [[Insulin secretion|insulin exocytosis]]: the amplification requires a permissive rise in cytosolic calcium driven by glucose metabolism, which is the molecular basis of the glucose dependence that defines the class.{{r|drucker2018}} | 10 | Activation couples principally to G<sub>s</sub>, raising intracellular cAMP and activating protein kinase A and the exchange protein Epac2. In the pancreatic beta cell this cascade amplifies, but does not initiate, [[Insulin secretion|insulin exocytosis]]: the amplification requires a permissive rise in cytosolic calcium driven by glucose metabolism, which is the molecular basis of the glucose dependence that defines the class.{{r|drucker2018}} |
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| + | 12 | The receptor is expressed well beyond the pancreas, and the sites of expression explain much of the clinical profile of its agonists — gastric smooth muscle and enteric neurons for delayed [[Gastric emptying|emptying]], the area postrema for nausea, and hypothalamic [[Satiety signalling|satiety circuits]] for reduced food intake.{{r|graaf2016}} | |
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| 12 | == Structure and ligand engagement == | 14 | == Structure and ligand engagement == |
| 13 | GLP1R comprises an extracellular domain of about 130 residues, seven transmembrane helices and an intracellular C-terminal tail. Ligand binding follows the two-domain model characteristic of class B receptors: the C-terminal helix of the peptide is captured by the extracellular domain, which positions and concentrates the ligand, after which the peptide N-terminus inserts into a cavity formed by the transmembrane helices and drives the conformational change that couples to G protein.{{r|graaf2016}} | 15 | GLP1R comprises an extracellular domain of about 130 residues, seven transmembrane helices and an intracellular C-terminal tail. Ligand binding follows the two-domain model characteristic of class B receptors: the C-terminal helix of the peptide is captured by the extracellular domain, which positions and concentrates the ligand, after which the peptide N-terminus inserts into a cavity formed by the transmembrane helices and drives the conformational change that couples to G protein.{{r|graaf2016}} |