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amylin; islet amyloid polypeptide; diabetes-associated peptide; DAP; insulinoma amyloid peptide (IAPP)
Function:
1) synergistic with insulin in lowering plasma glucose
2) reduces food intake, delays gastric emptying, inhibits secretion of digestive juices (gastric acid, pancreatic enzymes, bile)
3) inhibits secretion of glucagon
4) some effects occur via recognition of amylin by receptors in the area postrema of the brain stem
5) effects of amylin may be over-ridden during times of hypoglycemia
6) selectively inhibits insulin-stimulated glucose utilization & glycogen deposition in muscle
7) does not affect adipocyte glucose metabolism
8) also acts in bone metabolism along with calcitonin & CGRP
a) can elicit hypocalcemic effects of calcitonin
b) can elicit vasodilator effects of CGRP
9) amylin is degraded, in part, by insulin-degrading enzyme
Structure:
- 37 residue polypeptide
- amylin is 46% homologous to beta-CGRP
Compartment: secreted
Expression:
- secreted by pancreatic beta-cells at the same time as insulin; stoichiometry roughly 1 amylin to 100 insulin
Pharmacology:
1) pramlintide (Symlin) is a synthetic amylin indicated for reducing insulin requirements in type 1 & type 2 diabetics
Pathology:
1) IAPP is the peptide subunit of amyloid found in pancreatic islets of type 2 diabetic patients & in patients with insulinomas
2) an increased secretion of amylin by beta cells may predispose to amyloid deposition & inhibit action of insulin in peripheral tissues
3) amylin-containing amyloid may result in cell-death of islet beta-cells
Specific
pramlintide (Symlin)
General
amyloid
secreted peptide
Properties
SIZE: entity length = 89 aa
MW = 10 kD
COMPARTMENT: extracellular compartment
MOTIF: signal sequence {1-22}
cysteine residue {C35}
MODIFICATION: cysteine residue {C40}
cysteine residue {C40}
MODIFICATION: cysteine residue {C35}
Database Correlations
OMIM 147940
UniProt P10997
Pfam PF00214
Entrez Gene 3375
Kegg hsa:3375
References
- Rink TJ et al
Structure and biology of amylin
TIPS 14:113 1993
PMID: 8516954
- OMIM :accession 147940
- UniProt :accession P10997
- Wikipedia: Amylin
http://en.wikipedia.org/wiki/Amylin