Insulin secretion: difference between revisions
Diff·revision 5 → 6·09:31, 28 Sep 2024
Difference between revision 5 and revision 6 of Insulin secretion. 8 lines changed; the page grew by 1,094 bytes.
| Revision 5 — 05:15, 15 Sep 2024 DeadSpaceDot (talk) the numbers in the lead disagreed with the body; body was right 2,712 bytes +352 | Revision 6 — 09:31, 28 Sep 2024 CuriousCallum (talk) name the enzyme responsible for the cleavage at the first mention 3,806 bytes +1,094 | ||
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| 17 | 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}} | 17 | 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}} |
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| + | 19 | The dose-response between glucose and secretion is sigmoid, with a threshold near 5 mM and a half-maximal response near 8 mM. Below the threshold the amplifying pathways have essentially nothing to amplify — the mechanistic statement of what "glucose-dependent" means in the incretin literature. | |
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| + | 21 | == Amplifying pathways == | |
| + | 22 | Amplification acts on the efficiency of the exocytotic machinery rather than on the trigger. The best characterised amplifier is cAMP, generated when [[GLP-1 receptor|GLP-1]] or GIP receptors couple to G<sub>s</sub>. cAMP acts through protein kinase A and through the exchange protein Epac2, which increases the number of granules released per unit of calcium influx.{{r|drucker2018}} | |
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| + | 24 | Metabolic amplification independent of cAMP also exists: at fixed calcium, raising glucose still increases secretion, an effect attributed to mitochondrially derived coupling factors including NADPH and glutamate. This pathway accounts for a substantial fraction of the total glucose response and is not fully characterised.{{r|rorsman2013}} | |
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| 19 | == References == | 26 | == References == |
| 20 | {{reflist}} | 27 | {{reflist}} |
| ⋮ | ⋮ | ||
| 25 | [[Category:Incretin biology]] | 32 | [[Category:Incretin biology]] |
| 26 | [[Category:Receptor pharmacology]] | 33 | [[Category:Receptor pharmacology]] |
| + | 34 | [[Category:Compounds and pharmacology]] | |
| 27 | 35 |