Amylin (revision 13)
Old revision·00:57, 17 Jan 2025·FmocFrancis
| AmylinIslet hormone | |
|---|---|
| Also known as | Islet amyloid polypeptide (IAPP) |
| Source | Pancreatic beta cell, co-secreted with insulin |
| Residues | 37 |
| Properties | |
| Molar mass | ≈3,903 g·mol⁻¹ |
| Plasma half-life | ≈13 minutes |
| Notable property | Human sequence is amyloidogenic |
| Receptor | |
| Target | Calcitonin receptor plus RAMP1/2/3 |
| Principal site | Area postrema |
| Compound infobox · conventions | |
Amylin, also called islet amyloid polypeptide (IAPP), is a 37-residue peptide hormone stored in the same secretory granules as insulin and released with it in an approximately 1:20 molar ratio. Its physiological actions are complementary to those of insulin: it slows gastric emptying, suppresses postprandial glucagon secretion, and promotes satiety.[1]
Amylin does not have a dedicated receptor. It acts at the calcitonin receptor in complex with one of three receptor-activity-modifying proteins, RAMP1, RAMP2 or RAMP3, which together constitute the AMY1, AMY2 and AMY3 receptors. The principal site of action for the satiety effect is the area postrema, outside the blood-brain barrier.[1]
The human sequence is amyloidogenic: it aggregates into fibrils, and islet amyloid deposits derived from it are found in the pancreas in most people with long-standing type 2 diabetes. This property made native amylin undevelopable as a medicine and forced the design of non-aggregating analogues; see Amylin receptor agonist.[2]
Physiology
[edit]Amylin is co-packaged with insulin in the beta-cell secretory granule and released by the same stimuli, so its plasma profile mirrors that of insulin. Fasting concentrations are in the low picomolar range and rise several-fold after a meal.[1]
Its three principal actions all restrain nutrient entry rather than promoting disposal. Gastric emptying slows, which flattens the postprandial glucose excursion. Glucagon secretion is suppressed in the postprandial state — but not during hypoglycaemia, where counter-regulation is preserved. Food intake falls through hindbrain signalling that is distinct from, and additive to, the GLP-1 satiety pathway.
Because insulin and amylin are co-secreted, amylin deficiency accompanies insulin deficiency: in type 1 diabetes both are essentially absent, and this contributes to the exaggerated postprandial glucose excursions seen when insulin is replaced alone.[1][3]
Receptors
[edit]The amylin receptors are heterodimers of the calcitonin receptor with a RAMP. The RAMP does not merely traffic the receptor; it alters the ligand-binding pocket, converting a calcitonin receptor into one with high affinity for amylin.
| Complex | Components | Note |
|---|---|---|
| AMY1 | CTR + RAMP1 | Highest amylin affinity; area postrema |
| AMY2 | CTR + RAMP2 | Less well characterised |
| AMY3 | CTR + RAMP3 | Widely distributed |
See also
References
- ^ a b c d Hay DL, Chen S, Lutz TA, Parkes DG, Roth JD. "Amylin: pharmacology, physiology, and clinical potential." Pharmacological Reviews 67(3):564–600 (2015). DOI:10.1124/pr.115.010629. PMID 26071095.
- ^ Westermark P, Andersson A, Westermark GT. "Islet amyloid polypeptide, islet amyloid, and diabetes mellitus." Physiological Reviews 91(3):795–826 (2011). DOI:10.1152/physrev.00042.2009. PMID 21742788.
- ^ Campbell JE, Drucker DJ. "Pharmacology, physiology, and mechanisms of incretin hormone action." Cell Metabolism 17(6):819–837 (2013). PMID 23684623.