Glucagon: difference between revisions
Diff·revision 4 → 5·04:36, 30 Aug 2024
Difference between revision 4 and revision 5 of Glucagon. 4 lines changed; the page grew by 683 bytes.
| Revision 4 — 22:30, 11 Aug 2024 RetatrutideRuben (talk) expand §Secretion and its control 2,758 bytes ±0 | Revision 5 — 04:36, 30 Aug 2024 MazdutideMads (talk) convert the substitution list to a table so the analogues line up 3,441 bytes +683 | ||
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| 10 | Glucagon has been used clinically for decades as rescue treatment for severe [[Hypoglycaemia|hypoglycaemia]] and as a smooth-muscle relaxant for gastrointestinal imaging. Its more recent interest to this wiki is as a deliberate pharmacological target: agonism at the glucagon receptor increases energy expenditure and hepatic fat oxidation, and several investigational peptides combine it with [[GLP-1 receptor agonist|GLP-1 agonism]] so that the glycaemic penalty is offset.{{r|coskun2022}} | 10 | Glucagon has been used clinically for decades as rescue treatment for severe [[Hypoglycaemia|hypoglycaemia]] and as a smooth-muscle relaxant for gastrointestinal imaging. Its more recent interest to this wiki is as a deliberate pharmacological target: agonism at the glucagon receptor increases energy expenditure and hepatic fat oxidation, and several investigational peptides combine it with [[GLP-1 receptor agonist|GLP-1 agonism]] so that the glycaemic penalty is offset.{{r|coskun2022}} |
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| + | 12 | Hyperglucagonaemia is a feature of type 2 diabetes and contributes to fasting hyperglycaemia through unrestrained hepatic glucose output. Suppression of glucagon secretion is one of the mechanisms by which incretin-based therapies lower fasting glucose, and it is glucose-dependent — suppression relaxes as glucose falls, which is part of why those therapies do not by themselves cause hypoglycaemia.{{r|sandoval2015}} | |
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| 12 | == Secretion and its control == | 14 | == Secretion and its control == |
| 13 | Alpha cells constitute roughly 30–40% of the human islet and are distributed throughout it rather than confined to a mantle as in rodents. Secretion is stimulated by hypoglycaemia, by adrenergic input during stress and exercise, and by amino acids — a protein meal raises both insulin and glucagon, which is teleologically sensible since the insulin response would otherwise produce hypoglycaemia.{{r|sandoval2015}} | 15 | Alpha cells constitute roughly 30–40% of the human islet and are distributed throughout it rather than confined to a mantle as in rodents. Secretion is stimulated by hypoglycaemia, by adrenergic input during stress and exercise, and by amino acids — a protein meal raises both insulin and glucagon, which is teleologically sensible since the insulin response would otherwise produce hypoglycaemia.{{r|sandoval2015}} |
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| 15 | Suppression of glucagon is mediated by several converging signals: direct glucose sensing by the alpha cell, paracrine inhibition by insulin, somatostatin and zinc from neighbouring cells, and incretin action. GLP-1 suppresses glucagon secretion; GIP, in contrast, stimulates it at euglycaemia while remaining neutral or suppressive at hyperglycaemia. This difference is one of the more interesting unresolved points in the pharmacology of dual agonists.{{r|campbell2013}} | 17 | Suppression of glucagon is mediated by several converging signals: direct glucose sensing by the alpha cell, paracrine inhibition by insulin, somatostatin and zinc from neighbouring cells, and incretin action. GLP-1 suppresses glucagon secretion; GIP, in contrast, stimulates it at euglycaemia while remaining neutral or suppressive at hyperglycaemia. This difference is one of the more interesting unresolved points in the pharmacology of dual agonists.{{r|campbell2013}} |
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| + | 19 | In type 1 diabetes the alpha-cell response to hypoglycaemia is lost early, which removes the first line of defence against insulin-induced hypoglycaemia and is a principal reason that condition is harder to manage than the pathophysiology alone would suggest. | |
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| 17 | == References == | 21 | == References == |