Glucagon-like peptide-1: difference between revisions
Diff·revision 33 → 34·17:10, 18 Dec 2024
Difference between revision 33 and revision 34 of Glucagon-like peptide-1. 11 lines changed; the page grew by 1,717 bytes.
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| 56 | The consequence is a plasma half-life of approximately 1.5–2 minutes, and an estimated 50–75% of newly secreted GLP-1 is degraded before it leaves the intestinal capillary bed. Two therapeutic strategies follow directly from this: inhibit the enzyme, which is the mechanism of the gliptin class, or engineer the peptide so that it resists the enzyme, which is the mechanism of the [[GLP-1 receptor agonist|agonist class]].{{r|nauck2018}} | 56 | The consequence is a plasma half-life of approximately 1.5–2 minutes, and an estimated 50–75% of newly secreted GLP-1 is degraded before it leaves the intestinal capillary bed. Two therapeutic strategies follow directly from this: inhibit the enzyme, which is the mechanism of the gliptin class, or engineer the peptide so that it resists the enzyme, which is the mechanism of the [[GLP-1 receptor agonist|agonist class]].{{r|nauck2018}} |
| 57 | 57 | ||
| + | 58 | Substitution at position 8 — alanine to aminoisobutyric acid in [[tirzepatide]], or to 2-aminoisobutyric acid in several other constructs — is the most common resistance strategy, usually combined with [[Albumin binding half-life extension|albumin-binding acylation]] to slow renal clearance. | |
| + | 59 | ||
| + | 60 | == Physiological actions == | |
| + | 61 | ; Insulinotropic action : GLP-1 amplifies glucose-stimulated insulin secretion. The effect is strictly glucose-dependent: at euglycaemia, GLP-1 infusion produces little insulin release, which is the basis of the low intrinsic [[Hypoglycaemia|hypoglycaemia]] risk of the drug class in the absence of insulin or sulfonylurea co-therapy.{{r|holst2007}} | |
| + | 62 | ; Glucagon suppression : Postprandial glucagon secretion is reduced, again in a glucose-dependent manner, contributing to lower hepatic glucose output. | |
| + | 63 | ; Gastric emptying : Emptying of solids and liquids is slowed, flattening postprandial glucose excursions and contributing to both satiety and the class's [[Adverse effects of GLP-1 receptor agonists|gastrointestinal adverse effects]].{{r|drucker2018}} | |
| + | 64 | ; Central effects : GLP-1 receptors in the [[Arcuate nucleus|arcuate nucleus]], area postrema and nucleus tractus solitarius mediate reductions in food intake. Peripherally administered agonists reach these sites in part through regions of incomplete blood–brain barrier. | |
| + | 65 | ||
| + | 66 | Actions on the heart, kidney, liver and immune system have all been described, and cardiovascular and renal benefit has been demonstrated for several agonists in outcome trials; the extent to which those benefits are receptor-mediated rather than secondary to weight and glycaemic change remains an open question.{{r|drucker2018}} | |
| + | 67 | ||
| 58 | == References == | 68 | == References == |
| 59 | {{reflist}} | 69 | {{reflist}} |
| ⋮ | ⋮ | ||
| 72 | * [[Incretin effect]] | 82 | * [[Incretin effect]] |
| 73 | * [[Dipeptidyl peptidase-4]] | 83 | * [[Dipeptidyl peptidase-4]] |
| + | 84 | * [[GLP-1 receptor agonist]] | |
| 74 | 85 | ||
| 75 | {{DEFAULTSORT:Glucagon-like peptide-1}} | 86 | {{DEFAULTSORT:Glucagon-like peptide-1}} |