Amylin

This article is about the polypeptide. For the defunct biotechnology company, see Amylin Pharmaceuticals.

Amylin, or islet amyloid polypeptide (IAPP), is a 37-residue peptide hormone.^[5] It is co-secreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1 (insulin:amylin). Amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels.

IAPP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1KUW, 2G48, 2KB8, 2L86, 3FPO, 3FR1, 3FTH, 3FTK, 3FTL, 3FTR, 3G7V, 3G7W, 3HGZ, 3DG1
Identifiers
Aliases	IAPP, DAP, IAP, islet amyloid polypeptide
External IDs	OMIM: 147940 MGI: 96382 HomoloGene: 36024 GeneCards: IAPP
Gene location (Human) Chr. Chromosome 12 (human)^[1] Band 12p12.1 Start 21,354,959 bp^[1] End 21,379,980 bp^[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)^[2] Band 6 G2|6 73.81 cM Start 142,244,149 bp^[2] End 142,249,687 bp^[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in islet of Langerhans body of pancreas right lobe of liver duodenum bone marrow breast mesencephalon urinary system substantia nigra lymph node Top expressed in islet of Langerhans pyloric antrum Paneth cell supraoptic nucleus jejunum crypt of lieberkuhn of small intestine duodenum conjunctival fornix thymus ileum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function signaling receptor binding hormone activity identical protein binding amyloid-beta binding protein binding Cellular component extracellular region neuronal cell body extracellular space inclusion body Biological process negative regulation of cell differentiation cell-cell signaling sensory perception of pain eating behavior signal transduction negative regulation of bone resorption apoptotic process negative regulation of cell population proliferation protein destabilization protein homooligomerization amyloid fibril formation G protein-coupled receptor signaling pathway adenylate cyclase-activating G protein-coupled receptor signaling pathway positive regulation of cytosolic calcium ion concentration regulation of signaling receptor activity positive regulation of protein kinase A signaling negative regulation of mitochondrion organization negative regulation of protein homooligomerization positive regulation of apoptotic process positive regulation of MAPK cascade positive regulation of protein kinase B signaling amylin receptor signaling pathway negative regulation of amyloid fibril formation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3375 15874 Ensembl ENSG00000121351 ENSMUSG00000041681 UniProt P10997 P12968 RefSeq (mRNA) NM_000415 NM_001329201 NM_010491 RefSeq (protein) NP_000406 NP_001316130 NP_034621 Location (UCSC) Chr 12: 21.35 – 21.38 Mb Chr 6: 142.24 – 142.25 Mb PubMed search ^[3] ^[4]
Wikidata
View/Edit Human View/Edit Mouse

Amino acid sequence of amylin with disulfide bridge and cleavage sites of insulin degrading enzyme indicated with arrows

IAPP is processed from an 89-residue coding sequence. Proislet amyloid polypeptide (proIAPP, proamylin, proislet protein) is produced in the pancreatic beta cells (β-cells) as a 67 amino acid, 7404 Dalton pro-peptide and undergoes post-translational modifications including protease cleavage to produce amylin.^[6]

Synthesis

ProIAPP consists of 67 amino acids, which follow a 22 amino acid signal peptide which is rapidly cleaved after translation of the 89 amino acid coding sequence. The human sequence (from N-terminus to C-terminus) is:

(MGILKLQVFLIVLSVALNHLKA) TPIESHQVEKR^ KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTYG^ KR^ NAVEVLKREPLNYLPL.^[6][7] The signal peptide is removed during translation of the protein and transport into the endoplasmic reticulum. Once inside the endoplasmic reticulum, a disulfide bond is formed between cysteine residues numbers 2 and 7.^[8] Later in the secretory pathway, the precursor undergoes additional proteolysis and posttranslational modification (indicated by ^). 11 amino acids are removed from the N-terminus by the enzyme proprotein convertase 2 (PC2) while 16 are removed from the C-terminus of the proIAPP molecule by proprotein convertase 1/3 (PC1/3).^[9] At the C-terminus Carboxypeptidase E then removes the terminal lysine and arginine residues.^[10] The terminal glycine amino acid that results from this cleavage allows the enzyme peptidylglycine alpha-amidating monooxygenase (PAM) to add an amine group. After this the transformation from the precursor protein proIAPP to the biologically active IAPP is complete (IAPP sequence: KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY).^[6]

Regulation

Insofar as both IAPP and insulin are produced by the pancreatic β-cells, impaired β-cell function (due to lipotoxicity and glucotoxicity) will affect both insulin and IAPP production and release.^[11]

Insulin and IAPP are regulated by similar factors since they share a common regulatory promoter motif.^[12] The IAPP promoter is also activated by stimuli which do not affect insulin, such as tumor necrosis factor alpha^[13] and fatty acids.^[14] One of the defining features of Type 2 diabetes is insulin resistance. This is a condition wherein the body is unable to utilize insulin effectively, resulting in increased insulin production; since proinsulin and proIAPP are cosecreted, this results in an increase in the production of proIAPP as well. Although little is known about IAPP regulation, its connection to insulin indicates that regulatory mechanisms that affect insulin also affect IAPP. Thus blood glucose levels play an important role in regulation of proIAPP synthesis.

Function

Amylin functions as part of the endocrine pancreas and contributes to glycemic control. The peptide is secreted from the pancreatic islets into the blood circulation and is cleared by peptidases in the kidney. It is not found in the urine.

Amylin's metabolic function is well-characterized as an inhibitor of the appearance of nutrient [especially glucose] in the plasma.^[15] It thus functions as a synergistic partner to insulin, with which it is cosecreted from pancreatic beta cells in response to meals. The overall effect is to slow the rate of appearance (Ra) of glucose in the blood after eating; this is accomplished via coordinate slowing down gastric emptying, inhibition of digestive secretion [gastric acid, pancreatic enzymes, and bile ejection], and a resulting reduction in food intake. Appearance of new glucose in the blood is reduced by inhibiting secretion of the gluconeogenic hormone glucagon. These actions, which are mostly carried out via a glucose-sensitive part of the brain stem, the area postrema, may be over-ridden during hypoglycemia. They collectively reduce the total insulin demand.^[16]

Amylin also acts in bone metabolism, along with the related peptides calcitonin and calcitonin gene related peptide.^[15]

Rodent amylin knockouts do not have a normal reduction of appetite following food consumption.^{[citation needed]} Because it is an amidated peptide, like many neuropeptides, it is believed to be responsible for the effect on appetite.

Structure

The human form of IAPP has the amino acid sequence KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY, with a disulfide bridge between cysteine residues 2 and 7. Both the amidated C-terminus and the disulfide bridge are necessary for the full biological activity of amylin.^[8] IAPP is capable of forming amyloid fibrils in vitro. Within the fibrillization reaction, the early prefibrillar structures are extremely toxic to beta-cell and insuloma cell cultures.^[8] Later amyloid fiber structures also seem to have some cytotoxic effect on cell cultures. Studies have shown that fibrils are the end product and not necessarily the most toxic form of amyloid proteins/peptides in general. A non-fibril forming peptide (1–19 residues of human amylin) is toxic like the full-length peptide but the respective segment of rat amylin is not.^[17][18][19] It was also demonstrated by solid-state NMR spectroscopy that the fragment 20-29 of the human-amylin fragments membranes.^[20] Rats and mice have six substitutions (three of which are proline substitutions at positions 25, 28 and 29) that are believed to prevent the formation of amyloid fibrils, although not completely as seen by its propensity to form amyloid fibrils in vitro.^[21][22] Rat IAPP is nontoxic to beta-cells when overexpressed in transgenic rodents.

History

Before amylin deposition was associated with diabetes, already in 1901, scientists described the phenomenon of "islet hyalinization", which could be found in some cases of diabetes.^[23][24] A thorough study of this phenomenon was possible much later. In 1986, the isolation of an aggregate from an insulin-producing tumor was successful, a protein called IAP (Insulinoma Amyloid Peptide) was characterized, and amyloids were isolated from the pancreas of a diabetic patient, but the isolated material was not sufficient for full characterization.^[25] This was achieved only a year later by two research teams whose research was a continuation of the work from 1986.^[26][27]

Clinical significance

ProIAPP has been linked to Type 2 diabetes and the loss of islet β-cells.^[28] Islet amyloid formation, initiated by the aggregation of proIAPP, may contribute to this progressive loss of islet β-cells. It is thought that proIAPP forms the first granules that allow for IAPP to aggregate and form amyloid which may lead to amyloid-induced apoptosis of β-cells.

IAPP is cosecreted with insulin. Insulin resistance in Type 2 diabetes produces a greater demand for insulin production which results in the secretion of proinsulin.^[29] ProIAPP is secreted simultaneously, however, the enzymes that convert these precursor molecules into insulin and IAPP, respectively, are not able to keep up with the high levels of secretion, ultimately leading to the accumulation of proIAPP.

In particular, the impaired processing of proIAPP that occurs at the N-terminal cleavage site is a key factor in the initiation of amyloid.^[29] Post-translational modification of proIAPP occurs at both the carboxy terminus and the amino terminus, however, the processing of the amino terminus occurs later in the secretory pathway. This might be one reason why it is more susceptible to impaired processing under conditions where secretion is in high demand.^[10] Thus, the conditions of Type 2 diabetes—high glucose concentrations and increased secretory demand for insulin and IAPP—could lead to the impaired N-terminal processing of proIAPP. The unprocessed proIAPP can then serve as the nucleus upon which IAPP can accumulate and form amyloid.^[30]

The amyloid formation might be a major mediator of apoptosis, or programmed cell death, in the islet β-cells.^[30] Initially, the proIAPP aggregates within secretory vesicles inside the cell. The proIAPP acts as a seed, collecting matured IAPP within the vesicles, forming intracellular amyloid. When the vesicles are released, the amyloid grows as it collects even more IAPP outside the cell. The overall effect is an apoptosis cascade initiated by the influx of ions into the β-cells.

 

General Scheme for Amyloid Formation

In summary, impaired N-terminal processing of proIAPP is an important factor initiating amyloid formation and β-cell death. These amyloid deposits are pathological characteristics of the pancreas in Type 2 diabetes. However, it is still unclear as to whether amyloid formation is involved in or merely a consequence of type 2 diabetes.^[29] Nevertheless, it is clear that amyloid formation reduces working β-cells in patients with Type 2 diabetes. This suggests that repairing proIAPP processing may help to prevent β-cell death, thereby offering hope as a potential therapeutic approach for Type 2 diabetes.

Amyloid deposits deriving from islet amyloid polypeptide (IAPP, or amylin) are commonly found in pancreatic islets of patients suffering diabetes mellitus type 2, or containing an insulinoma cancer. While the association of amylin with the development of type 2 diabetes has been known for some time,^{[citation needed]} its direct role as the cause has been harder to establish. Some studies suggest that amylin, like the related beta-amyloid (Abeta) associated with Alzheimer's disease, can induce apoptotic cell-death in insulin-producing beta cells, an effect that may be relevant to the development of type 2 diabetes.^[31]

A 2008 study reported a synergistic effect for weight loss with leptin and amylin coadministration in diet-induced obese rats by restoring hypothalamic sensitivity to leptin.^[32] However, in clinical trials, the study was halted at Phase 2 in 2011 when a problem involving antibody activity that might have neutralized the weight-loss effect of metreleptin in two patients who took the drug in a previously completed clinical study. The study combined metreleptin, a version of the human hormone leptin, and pramlintide, which is Amylin's diabetes drug Symlin, into a single obesity therapy.^[33] A proteomics study showed that human amylin shares common toxicity targets with beta-amyloid (Abeta), suggesting that type 2 diabetes and Alzheimer's disease share common toxicity mechanisms.^[34]

Pharmacology

A synthetic analog of human amylin with proline substitutions in positions 25, 26 and 29, or pramlintide (brand name Symlin), was approved in 2005 for adult use in patients with both diabetes mellitus type 1 and diabetes mellitus type 2. Insulin and pramlintide, injected separately but both before a meal, work together to control the post-prandial glucose excursion.^[35]

Amylin is degraded in part by insulin-degrading enzyme.^[36][37] Another long- acting analogue of Amylin is Cagrilintide being developed by Novo Nordisk ( now in the Phase 2 trials with the proposed brand name CagriSema co- formulated with Semaglutide as a once weekly subcutaneous injection ) as a measure to treat type II DM and obesity.

Receptors

There appear to be at least three distinct receptor complexes that amylin binds to with high affinity. All three complexes contain the calcitonin receptor at the core, plus one of three receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3.^[38]

See also

• carboxypeptidase E
• Pancreatic islets
• peptidylglycine alpha-amidating monooxygenase (PAM)
• Pramlintide
• proprotein convertase 1/3 (PC1/3)
• proprotein convertase 2 (PC2)
• Type II Diabetes

References

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13. Cai K, Qi D, Wang O, Chen J, Liu X, Deng B, et al. (March 2011). "TNF-α acutely upregulates amylin expression in murine pancreatic beta cells". Diabetologia. 54 (3): 617–626. doi:10.1007/s00125-010-1972-9. PMID 21116608.
14. Qi D, Cai K, Wang O, Li Z, Chen J, Deng B, et al. (January 2010). "Fatty acids induce amylin expression and secretion by pancreatic beta-cells". American Journal of Physiology. Endocrinology and Metabolism. 298 (1): E99–E107. doi:10.1152/ajpendo.00242.2009. PMID 19843871.
15. Pittner RA, Albrandt K, Beaumont K, Gaeta LS, Koda JE, Moore CX, et al. (1994). "Molecular physiology of amylin". Journal of Cellular Biochemistry. 55 (Suppl): 19–28. doi:10.1002/jcb.240550004. PMID 7929615. S2CID 35842871.
16. Ratner RE, Dickey R, Fineman M, Maggs DG, Shen L, Strobel SA, et al. (November 2004). "Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial". Diabetic Medicine. 21 (11): 1204–1212. doi:10.1111/j.1464-5491.2004.01319.x. PMID 15498087. S2CID 23236294.
17. Brender JR, Lee EL, Cavitt MA, Gafni A, Steel DG, Ramamoorthy A (May 2008). "Amyloid fiber formation and membrane disruption are separate processes localized in two distinct regions of IAPP, the type-2-diabetes-related peptide". Journal of the American Chemical Society. 130 (20): 6424–6429. doi:10.1021/ja710484d. PMC 4163023. PMID 18444645.
18. Brender JR, Hartman K, Reid KR, Kennedy RT, Ramamoorthy A (December 2008). "A single mutation in the nonamyloidogenic region of islet amyloid polypeptide greatly reduces toxicity". Biochemistry. 47 (48): 12680–12688. doi:10.1021/bi801427c. PMC 2645932. PMID 18989933.
19. Nanga RP, Brender JR, Xu J, Veglia G, Ramamoorthy A (December 2008). "Structures of rat and human islet amyloid polypeptide IAPP(1-19) in micelles by NMR spectroscopy". Biochemistry. 47 (48): 12689–12697. doi:10.1021/bi8014357. PMC 2953382. PMID 18989932.
20. Brender JR, Dürr UH, Heyl D, Budarapu MB, Ramamoorthy A (September 2007). "Membrane fragmentation by an amyloidogenic fragment of human Islet Amyloid Polypeptide detected by solid-state NMR spectroscopy of membrane nanotubes". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1768 (9): 2026–2029. doi:10.1016/j.bbamem.2007.07.001. PMC 2042489. PMID 17662957.
21. Palmieri LC, Melo-Ferreira B, Braga CA, Fontes GN, Mattos LJ, Lima LM (2013). "Stepwise oligomerization of murine amylin and assembly of amyloid fibrils". Biophysical Chemistry. 180–181: 135–144. doi:10.1016/j.bpc.2013.07.013. PMID 23974296.
22. Erthal LC, Marques AF, Almeida FC, Melo GL, Carvalho CM, Palmieri LC, et al. (November 2016). "Regulation of the assembly and amyloid aggregation of murine amylin by zinc". Biophysical Chemistry. 218: 58–70. doi:10.1016/j.bpc.2016.09.008. PMID 27693831.
23. Opie EL (January 1901). "On the Relation of Chronic Interstitial Pancreatitis to the Islands of Langerhans and to Diabetes Melutus". The Journal of Experimental Medicine. 5 (4): 397–428. doi:10.1084/jem.5.4.397. PMC 2118050. PMID 19866952.
24. Hensel H (March 1932). "Beiträge zur Kenntnis des Feineren Baues der Schilddrüse der Neunaugenlarven". Zeitschrift für Zellforschung und Mikroskopische Anatomie. 15 (1): 1–35. doi:10.1007/978-3-662-29315-7. ISBN 978-3-662-27815-4.
25. Westermark P, Wernstedt C, Wilander E, Sletten K (November 1986). "A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas". Biochemical and Biophysical Research Communications. 140 (3): 827–831. doi:10.1016/0006-291x(86)90708-4. PMID 3535798.
26. Cooper GJ, Willis AC, Clark A, Turner RC, Sim RB, Reid KB (December 1987). "Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients". Proceedings of the National Academy of Sciences of the United States of America. 84 (23): 8628–8632. Bibcode:1987PNAS...84.8628C. doi:10.1073/pnas.84.23.8628. PMC 299599. PMID 3317417.
27. Westermark P, Wernstedt C, Wilander E, Hayden DW, O'Brien TD, Johnson KH (June 1987). "Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells". Proceedings of the National Academy of Sciences of the United States of America. 84 (11): 3881–3885. Bibcode:1987PNAS...84.3881W. doi:10.1073/pnas.84.11.3881. PMC 304980. PMID 3035556.
28. Paulsson JF, Westermark GT (July 2005). "Aberrant processing of human proislet amyloid polypeptide results in increased amyloid formation". Diabetes. 54 (7): 2117–2125. doi:10.2337/diabetes.54.7.2117. PMID 15983213.
29. Marzban L, Rhodes CJ, Steiner DF, Haataja L, Halban PA, Verchere CB (August 2006). "Impaired NH2-terminal processing of human proislet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death". Diabetes. 55 (8): 2192–2201. doi:10.2337/db05-1566. PMID 16873681.
30. Paulsson JF, Andersson A, Westermark P, Westermark GT (June 2006). "Intracellular amyloid-like deposits contain unprocessed pro-islet amyloid polypeptide (proIAPP) in beta cells of transgenic mice overexpressing the gene for human IAPP and transplanted human islets". Diabetologia. 49 (6): 1237–1246. doi:10.1007/s00125-006-0206-7. PMID 16570161.
31. Lorenzo A, Razzaboni B, Weir GC, Yankner BA (April 1994). "Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus". Nature. 368 (6473): 756–760. Bibcode:1994Natur.368..756L. doi:10.1038/368756a0. PMID 8152488. S2CID 4244347.
32. Roth JD, Roland BL, Cole RL, Trevaskis JL, Weyer C, Koda JE, et al. (May 2008). "Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies". Proceedings of the National Academy of Sciences of the United States of America. 105 (20): 7257–7262. Bibcode:2008PNAS..105.7257R. doi:10.1073/pnas.0706473105. PMC 2438237. PMID 18458326.
33. {{cite web] |title=Amylin and Takeda halt obesity drug study |url= https://www.pmlive.com/pharma_news/amylin_and_takeda_halt_obesity_drug_study_266050 | work = PMLive |date=17 March 2011}}
34. Lim YA, Rhein V, Baysang G, Meier F, Poljak A, Raftery MJ, et al. (April 2010). "Abeta and human amylin share a common toxicity pathway via mitochondrial dysfunction". Proteomics. 10 (8): 1621–1633. doi:10.1002/pmic.200900651. PMID 20186753. S2CID 33077667.
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Further reading

• Westermark P, Andersson A, Westermark GT (June 2005). "Is aggregated IAPP a cause of beta-cell failure in transplanted human pancreatic islets?". Current Diabetes Reports. 5 (3): 184–188. doi:10.1007/s11892-005-0007-2. PMID 15929864. S2CID 24682226.
• Höppener JW, Oosterwijk C, Visser-Vernooy HJ, Lips CJ, Jansz HS (December 1992). "Characterization of the human islet amyloid polypeptide/amylin gene transcripts: identification of a new polyadenylation site". Biochemical and Biophysical Research Communications. 189 (3): 1569–1577. doi:10.1016/0006-291X(92)90255-J. PMID 1282806.
• Hubbard JA, Martin SR, Chaplin LC, Bose C, Kelly SM, Price NC (May 1991). "Solution structures of calcitonin-gene-related-peptide analogues of calcitonin-gene-related peptide and amylin". The Biochemical Journal. 275 ( Pt 3) (Pt 3): 785–788. doi:10.1042/bj2750785. PMC 1150122. PMID 2039456.
• Butler PC, Chou J, Carter WB, Wang YN, Bu BH, Chang D, et al. (June 1990). "Effects of meal ingestion on plasma amylin concentration in NIDDM and nondiabetic humans". Diabetes. 39 (6): 752–756. doi:10.2337/diabetes.39.6.752. PMID 2189768.
• van Mansfeld AD, Mosselman S, Höppener JW, Zandberg J, van Teeffelen HA, Baas PD, et al. (October 1990). "Islet amyloid polypeptide: structure and upstream sequences of the IAPP gene in rat and man". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1087 (2): 235–240. doi:10.1016/0167-4781(90)90210-S. PMID 2223885.
• Christmanson L, Rorsman F, Stenman G, Westermark P, Betsholtz C (July 1990). "The human islet amyloid polypeptide (IAPP) gene. Organization, chromosomal localization and functional identification of a promoter region". FEBS Letters. 267 (1): 160–166. doi:10.1016/0014-5793(90)80314-9. PMID 2365085. S2CID 41096586.
• Clark A, Edwards CA, Ostle LR, Sutton R, Rothbard JB, Morris JF, Turner RC (July 1989). "Localisation of islet amyloid peptide in lipofuscin bodies and secretory granules of human B-cells and in islets of type-2 diabetic subjects". Cell and Tissue Research. 257 (1): 179–185. doi:10.1007/BF00221649. PMID 2546670. S2CID 22046812.
• Nishi M, Sanke T, Seino S, Eddy RL, Fan YS, Byers MG, et al. (November 1989). "Human islet amyloid polypeptide gene: complete nucleotide sequence, chromosomal localization, and evolutionary history". Molecular Endocrinology. 3 (11): 1775–1781. doi:10.1210/mend-3-11-1775. PMID 2608057.
• Mosselman S, Höppener JW, Lips CJ, Jansz HS (April 1989). "The complete islet amyloid polypeptide precursor is encoded by two exons". FEBS Letters. 247 (1): 154–158. doi:10.1016/0014-5793(89)81260-8. PMID 2651160. S2CID 45121588.
• Westermark P, Wernstedt C, Wilander E, Hayden DW, O'Brien TD, Johnson KH (June 1987). "Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells". Proceedings of the National Academy of Sciences of the United States of America. 84 (11): 3881–3885. Bibcode:1987PNAS...84.3881W. doi:10.1073/pnas.84.11.3881. PMC 304980. PMID 3035556.
• Mosselman S, Höppener JW, Zandberg J, van Mansfeld AD, Geurts van Kessel AH, Lips CJ, Jansz HS (November 1988). "Islet amyloid polypeptide: identification and chromosomal localization of the human gene". FEBS Letters. 239 (2): 227–232. doi:10.1016/0014-5793(88)80922-0. hdl:1874/23977. PMID 3181427. S2CID 26985644.
• Cooper GJ, Willis AC, Clark A, Turner RC, Sim RB, Reid KB (December 1987). "Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients". Proceedings of the National Academy of Sciences of the United States of America. 84 (23): 8628–8632. Bibcode:1987PNAS...84.8628C. doi:10.1073/pnas.84.23.8628. PMC 299599. PMID 3317417.
• Westermark P, Wernstedt C, Wilander E, Sletten K (November 1986). "A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas". Biochemical and Biophysical Research Communications. 140 (3): 827–831. doi:10.1016/0006-291X(86)90708-4. PMID 3535798.
• Höppener JW, Verbeek JS, de Koning EJ, Oosterwijk C, van Hulst KL, Visser-Vernooy HJ, et al. (December 1993). "Chronic overproduction of islet amyloid polypeptide/amylin in transgenic mice: lysosomal localization of human islet amyloid polypeptide and lack of marked hyperglycaemia or hyperinsulinaemia". Diabetologia. 36 (12): 1258–1265. doi:10.1007/BF00400803. PMID 8307253.
• Lim YA, Ittner LM, Lim YL, Götz J (June 2008). "Human but not rat amylin shares neurotoxic properties with Abeta42 in long-term hippocampal and cortical cultures". FEBS Letters. 582 (15): 2188–2194. doi:10.1016/j.febslet.2008.05.006. PMID 18486611. S2CID 6201956.

External links

• amylin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• "Amylin Nucleation Site". PDB Entry 1KUW. RCSB Protein Data Bank. doi:10.2210/pdb1kuw/pdb. from the original on 16 April 2008. Retrieved 2008-05-28.
• Human DAP genome location and DAP gene details page in the UCSC Genome Browser.
• Human IAPP genome location and IAPP gene details page in the UCSC Genome Browser.