Insulin secretion: difference between revisions
Diff·revision 2 → 3·18:25, 21 Aug 2024
Difference between revision 2 and revision 3 of Insulin secretion. 5 lines changed; the page grew by 814 bytes.
| Revision 2 — 16:15, 7 Aug 2024 ReceptorRhoda (talk) correct the second-messenger pathway named in the lead 1,546 bytes ±0 | Revision 3 — 18:25, 21 Aug 2024 GsCouplingGil (talk) clarify that concentrations differ substantially between assay platforms 2,360 bytes +814 | ||
|---|---|---|---|
| 10 | The distinction between triggering and amplifying pathways is the single most important idea for understanding why [[GLP-1 receptor agonist|GLP-1 receptor agonists]] rarely cause [[Hypoglycaemia|hypoglycaemia]] while sulfonylureas frequently do. Sulfonylureas act on the triggering pathway and initiate secretion regardless of glucose; incretins act on the amplifying pathway and can only enlarge a response that glucose has already begun.{{r|drucker2018}} | 10 | The distinction between triggering and amplifying pathways is the single most important idea for understanding why [[GLP-1 receptor agonist|GLP-1 receptor agonists]] rarely cause [[Hypoglycaemia|hypoglycaemia]] while sulfonylureas frequently do. Sulfonylureas act on the triggering pathway and initiate secretion regardless of glucose; incretins act on the amplifying pathway and can only enlarge a response that glucose has already begun.{{r|drucker2018}} |
| 11 | 11 | ||
| + | 12 | == The triggering pathway == | |
| + | 13 | Glucose enters the beta cell through GLUT1 and GLUT3 transporters and is phosphorylated by glucokinase, whose kinetics — a high {{math|K_m}} near 8 mM and no product inhibition — make it the rate-limiting step and the cell's effective glucose sensor. Subsequent glycolysis and mitochondrial oxidation raise the cytosolic ATP:ADP ratio.{{r|rorsman2013}} | |
| + | 14 | ||
| + | 15 | The rise in ATP:ADP closes ATP-sensitive potassium channels. The membrane depolarises, voltage-gated calcium channels open, cytosolic calcium rises, and the calcium rise triggers exocytosis of insulin granules. Sulfonylureas close the same potassium channel pharmacologically, which is why their action is glucose-independent, and loss-of-function mutations in the channel produce congenital hyperinsulinism.{{r|rorsman2013}} | |
| + | 16 | ||
| 12 | == References == | 17 | == References == |
| 13 | {{reflist}} | 18 | {{reflist}} |