View source for Amylin

{{About|the polypeptide|the biotechnology company|Amylin Pharmaceuticals}}
{{Infobox_gene}}
[[Image:Amylin primary structure.png|thumb|250px|right|Amino acid sequence of amylin with disulfide bridge and cleavage sites of insulin degrading enzyme indicated with arrows]]
'''Amylin,''' or '''islet amyloid polypeptide''' ('''IAPP'''), is a 37-residue [[peptide hormone]].<ref>{{cite web | title = Entrez Gene: IAPP islet amyloid polypeptide| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3375| accessdate = }}</ref>  It is cosecreted with [[insulin]] from the pancreatic [[beta cell|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 [[Postprandial|post-prandial]] spikes in blood glucose levels.

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.<ref name=Higham>{{cite journal | vauthors = Higham CE, Hull RL, Lawrie L, Shennan KI, Morris JF, Birch NP, Docherty K, Clark A | title = Processing of synthetic pro-islet amyloid polypeptide (proIAPP) 'amylin' by recombinant prohormone convertase enzymes, PC2 and PC3, in vitro | journal = Eur. J. Biochem. | volume = 267 | issue = 16 | pages = 4998–5004 |date=August 2000 | pmid = 10931181 | doi = 10.1046/j.1432-1327.2000.01548.x  }}</ref>

== Synthesis ==

[[Image:ProIAPP.jpg|thumb|Post-translational Modification of proIAPP to form IAPP]]

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.<ref name=Higham /><ref>{{cite web|url=https://www.ncbi.nlm.nih.gov/protein/NP_000406.1|title=islet amyloid polypeptide precursor [Homo sapiens]|publisher=NCBI}} (the current NCBI [[RefSeq]])</ref>
Once released from the signal peptide, it 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).<ref name=Sanke1988>{{cite journal | vauthors = Sanke T, Bell GI, Sample C, Rubenstein AH, Steiner DF | title = An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing | journal = J. Biol. Chem. | volume = 263 | issue = 33 | pages = 17243–6 |date=November 1988 | pmid = 3053705 | doi = | url = http://www.jbc.org/content/263/33/17243.long }}</ref>  At the C-terminus [[Carboxypeptidase E]] then removes the terminal [[lysine]] and [[arginine]] residues.<ref name=Marzban2005>{{cite journal |vauthors=Marzban L, Soukhatcheva G, Verchere CB | title = Role of carboxypeptidase E in processing of pro-islet amyloid polypeptide in {beta}-cells | journal = Endocrinology | volume = 146 | issue = 4 | pages = 1808–17 | date = April 2005 | pmid = 15618358 | doi = 10.1210/en.2004-1175 }}</ref> The terminal [[glycine]] amino acid that results from this cleavage allows the enzyme [[peptidylglycine alpha-amidating monooxygenase]] (PAM) to add an [[amine]] group. Finally, a [[disulfide]] bond is formed between [[cysteine]] residues numbers 2 and 7.<ref name=Roberts1989>{{cite journal | vauthors = Roberts AN, Leighton B, Todd JA, Cockburn D, Schofield PN, Sutton R, Holt S, Boyd Y, Day AJ, Foot EA | title = Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 86 | issue = 24 | pages = 9662–6 |date=December 1989 | pmid = 2690069 | pmc = 298561 | doi = 10.1073/pnas.86.24.9662  | bibcode = 1989PNAS...86.9662R  }}</ref> After this the transformation from the precursor protein proIAPP to the biologically active IAPP is complete (IAPP sequence: KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY).<ref name=Higham />

== Regulation ==

Insulin and IAPP are regulated by similar factors since they share a common regulatory [[Promoter (biology)|promoter]] motif.<ref name="pmid10933741">{{cite journal | vauthors = Höppener JW, Ahrén B, Lips CJ | title = Islet amyloid and type 2 diabetes mellitus | journal = N. Engl. J. Med. | volume = 343 | issue = 6 | pages = 411–9 |date=August 2000 | pmid = 10933741 | doi = 10.1056/NEJM200008103430607  }}</ref>  The IAPP promoter is also activated by stimuli which do not affect insulin, such as [[tumor necrosis factor alpha]]<ref name="pmid21116608">{{cite journal | vauthors = Cai K, Qi D, Wang O, Chen J, Liu X, Deng B, Qian L, Liu X, Le Y | title = TNF-α acutely upregulates amylin expression in murine pancreatic beta cells | journal = Diabetologia | volume = 54 | issue = 3 | pages = 617–26 |date=March 2011 | pmid = 21116608 | doi = 10.1007/s00125-010-1972-9 }}</ref> and [[fatty acids]].<ref name="pmid19843871">{{cite journal | vauthors = Qi D, Cai K, Wang O, Li Z, Chen J, Deng B, Qian L, Le Y | title = Fatty acids induce amylin expression and secretion by pancreatic beta-cells | journal = Am. J. Physiol. Endocrinol. Metab. | volume = 298 | issue = 1 | pages = E99–E107 |date=January 2010 | pmid = 19843871 | doi = 10.1152/ajpendo.00242.2009 }}</ref> 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.<ref name="Pittner_1994">{{cite journal | vauthors = Pittner RA, Albrandt K, Beaumont K, Gaeta LS, Koda JE, Moore CX, Rittenhouse J, Rink TJ | title = Molecular physiology of amylin | journal = J. Cell. Biochem. | volume = 55 Suppl | issue = | pages = 19–28 | year = 1994 | pmid = 7929615 | doi = 10.1002/jcb.240550004}}</ref> 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.<ref name="Ratner">{{cite journal |vauthors =Ratner RE, Dickey R, Fineman M, Maggs DG, Shen L, Strobel SA, Weyer C, Kolterman OG |title=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|journal=Diabet Med |volume= 21 |issue= 11|pages=1204–12 |year= 2004 | pmid = 15498087 |doi=10.1111/j.1464-5491.2004.01319.x}}</ref>

Amylin also acts in bone metabolism, along with the related peptides [[calcitonin]] and [[calcitonin gene related peptide]].<ref name="Pittner_1994"/>

Rodent amylin [[Gene knockout|knockout]]s do not have a normal [[anorexia (symptom)|reduction of appetite]] following food consumption.{{citation needed|date=August 2017}} Because it is an amidated peptide, like many [[neuropeptide]]s, 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.<ref name="Roberts1989" />  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.<ref name="Roberts1989" /> 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.<ref name="pmid18444645">{{cite journal | vauthors = Brender JR, Lee EL, Cavitt MA, Gafni A, Steel DG, Ramamoorthy A | title = Amyloid fiber formation and membrane disruption are separate processes localized in two distinct regions of IAPP, the type-2-diabetes-related peptide | journal = J. Am. Chem. Soc. | volume = 130 | issue = 20 | pages = 6424–9 |date=May 2008 | pmid = 18444645 | doi = 10.1021/ja710484d | pmc = 4163023 }}</ref><ref name="pmid18989933">{{cite journal | vauthors = Brender JR, Hartman K, Reid KR, Kennedy RT, Ramamoorthy A | title = A single mutation in the nonamyloidogenic region of islet amyloid polypeptide greatly reduces toxicity | journal = Biochemistry | volume = 47 | issue = 48 | pages = 12680–8 |date=December 2008 | pmid = 18989933 | pmc = 2645932 | doi = 10.1021/bi801427c }}</ref><ref name="pmid18989932">{{cite journal | vauthors = Nanga RP, Brender JR, Xu J, Veglia G, Ramamoorthy A | title = Structures of rat and human islet amyloid polypeptide IAPP(1-19) in micelles by NMR spectroscopy | journal = Biochemistry | volume = 47 | issue = 48 | pages = 12689–97 |date=December 2008 | pmid = 18989932 | pmc = 2953382 | doi = 10.1021/bi8014357 }}</ref> It was also demonstrated by solid-state NMR spectroscopy that the fragment 20-29 of the human-amylin fragments membranes.<ref name="pmid17662957">{{cite journal | vauthors = Brender JR, Dürr UH, Heyl D, Budarapu MB, Ramamoorthy A | title = Membrane Fragmentation by an Amyloidogenic Fragment of Human Islet Amyloid Polypeptide Detected by Solid-State NMR Spectroscopy of Membrane Nanotubes | journal = Biochim. Biophys. Acta | volume = 1768 | issue = 9 | pages = 2026–9 |date=September 2007 | pmid = 17662957 | pmc = 2042489 | doi = 10.1016/j.bbamem.2007.07.001 }}</ref> Rats and mice have six substitutions (three of which are proline substitions 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''.<ref>{{cite journal|authors= Palmieri, Leonardo C; Melo-Ferreira, Bruno; Braga, Carolina A; Fontes, Giselle N; Mattos, Luana J; Lima, Luis Mauricio|title=Stepwise oligomerization of murine amylin and assembly of amyloid fibrils|journal=Biophys Chem |date=2013 |volume=181|pages=135–144|doi=10.1016/j.bpc.2013.07.013|pmid=23974296|url=http://www.sciencedirect.com/science/article/pii/S0301462213001336}}</ref><ref>{{cite journal |authors=Erthal, Luiza C; Marques, Adriana F; Almeida, Fábio C; Melo, Gustavo L; Carvalho, Camila M; Palmieri, Leonardo C; Cabral, Kátia M; Fontes, Giselle N; Lima, Luis Mauricio |title=Regulation of the assembly and amyloid aggregation of murine amylin by zinc |journal=Biophys. Chem. |volume=218 |pages=58–70 |year=2016 |pmid=27693831 |doi=10.1016/j.bpc.2016.09.008|url=http://www.sciencedirect.com/science/article/pii/S030146221630182X}}</ref> Rat IAPP is nontoxic to beta-cells when overexpressed in transgenic rodents.

== History ==

IAPP was identified independently by two groups as the major component of [[diabetes]]-associated islet [[amyloid]] deposits in 1987.<ref name="Cooper">{{cite journal |vauthors =Cooper GJ, Willis AC, Clark A, Turner RC, Sim RB, Reid KB |title=Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients|journal=[[Proceedings of the National Academy of Sciences|Proc Natl Acad Sci USA]] |volume= 84 |issue= 23|pages=8628–32 |year= 1987 | pmid = 3317417 |doi=10.1073/pnas.84.23.8628 |pmc=299599|bibcode=1987PNAS...84.8628C}}</ref><ref name="Westermark">{{cite journal |vauthors =Westermark P, Wernstedt C, Wilander E, Hayden DW, O'Brien TD, Johnson KH |title=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|journal=[[Proceedings of the National Academy of Sciences|Proc Natl Acad Sci USA]] |volume= 84 |issue= 11|pages=3881–3885 |year= 1987 | pmid = 3035556 |doi=10.1073/pnas.84.11.3881 |pmc=304980 |bibcode=1987PNAS...84.3881W}}</ref>

The difference in nomenclature is largely geographical; European researchers tend to prefer IAPP whereas American researchers tend to prefer amylin.  Some researchers discourage the use of "amylin" on the grounds that it may be confused with the pharmaceutical company.{{Citation needed|date=August 2008}}

==Clinical significance==

ProIAPP has been linked to Type 2 diabetes and the loss of islet β-cells.<ref name=Paulsson2005>{{cite journal | vauthors = Paulsson JF, Westermark GT | title = Aberrant processing of human proislet amyloid polypeptide results in increased amyloid formation | journal = Diabetes | volume = 54 | issue = 7 | pages = 2117–25 |date=July 2005 | pmid = 15983213 | doi = 10.2337/diabetes.54.7.2117| url = }}</ref>  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.<ref name=Marzban2006>{{cite journal | vauthors = Marzban L, Rhodes CJ, Steiner DF, Haataja L, Halban PA, Verchere CB | title = Impaired NH2-terminal processing of human proislet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death | journal = Diabetes | volume = 55 | issue = 8 | pages = 2192–201 |date=August 2006 | pmid = 16873681 | doi = 10.2337/db05-1566 | url =  }}</ref>  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.<ref name=Marzban2006 /> 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.<ref name=Marzban2005 />  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 nidus upon which IAPP can accumulate and form amyloid.<ref name=Paulsson2006>{{cite journal | vauthors = Paulsson JF, Andersson A, Westermark P, Westermark GT | title = 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 | journal = Diabetologia | volume = 49 | issue = 6 | pages = 1237–46 |date=June 2006 | pmid = 16570161 | doi = 10.1007/s00125-006-0206-7 | url =  }}</ref>

The amyloid formation might be a major mediator of apoptosis, or programmed cell death, in the islet β-cells.<ref name=Paulsson2006 /> 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.

[[Image:Amyloid Formation.jpg|thumb|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.<ref name=Marzban2006 />  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 [[Islets of Langerhans|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,<ref name="pmid12221327">{{cite journal | author = Hayden MR | title = Islet amyloid, metabolic syndrome, and the natural progressive history of type 2 diabetes mellitus | journal = JOP | volume = 3 | issue = 5 | pages = 126–38 |date=September 2002 | pmid = 12221327 | doi = }}</ref> its direct role as the cause has been harder to establish.  Recent results suggest that amylin, like the related [[beta-amyloid]] (Abeta) associated with [[Alzheimer's disease]], can induce [[apoptosis|apoptotic cell-death]] in [[insulin]]-producing [[beta cells]], an effect that may be relevant to the development of type 2 diabetes.<ref name="pmid8152488">{{cite journal | vauthors = Lorenzo A, Razzaboni B, Weir GC, Yankner BA | title = Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus | journal = Nature | volume = 368 | issue = 6473 | pages = 756–60 |date=April 1994 | pmid = 8152488 | doi = 10.1038/368756a0  | bibcode = 1994Natur.368..756L }}</ref>

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.<ref name="pmid18458326">{{cite journal | vauthors = Roth JD, Roland BL, Cole RL, Trevaskis JL, Weyer C, Koda JE, Anderson CM, Parkes DG, Baron AD | title = Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 105 | issue = 20 | pages = 7257–62 |date=May 2008 | pmid = 18458326 | pmc = 2438237 | doi = 10.1073/pnas.0706473105 | bibcode = 2008PNAS..105.7257R }}</ref> 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.<ref>{{cite web|last=Darce|first=Keith|title=Amylin halts trial of weight-loss therapy|url=http://www.utsandiego.com/news/2011/mar/16/amlyn-halts-trial-weight-loss-therapy/}}</ref>  Finally, a recent proteomics study showed that human amylin shares common toxicity targets with [[beta-amyloid]] (Abeta), providing evidence that type 2 diabetes and Alzheimer's disease share common toxicity mechanisms.<ref name="pmid20186753">{{cite journal | vauthors = Lim YA, Rhein V, Baysang G, Meier F, Poljak A, Raftery MJ, Guilhaus M, Ittner LM, Eckert A, Götz J | title = Abeta and human amylin share a common toxicity pathway via mitochondrial dysfunction | journal = Proteomics | volume = 10 | issue = 8 | pages = 1621–33 |date=April 2010 | pmid = 20186753 | doi = 10.1002/pmic.200900651 }}</ref>

== Pharmacology ==

A synthetic analog of human amylin with proline substitutions in positions 25, 26 and 29, or pramlintide (brand name [[pramlintide|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.<ref name="urlAmylin">{{cite web | url = http://www.amylin.com/pipeline/symlin.cfm/ | title = SYMLIN (pramlintide acetate) | year = 2006 | format = | work = | publisher = Amylin Pharmaceuticals, Inc.| pages = | language = | quote = | accessdate = 2008-05-28| archiveurl= https://web.archive.org/web/20080613123046/http://www.amylin.com/pipeline/symlin.cfm/| archivedate= 13 June 2008 <!--DASHBot-->| deadurl= no}}</ref>

Amylin is degraded in part by [[insulin-degrading enzyme]].<ref name="pmid17051221">{{cite journal |vauthors=Shen Y, Joachimiak A, Rosner MR, Tang WJ | title = Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism | journal = Nature | volume = 443 | issue = 7113 | pages = 870–4 |date=October 2006 | pmid = 17051221 | doi = 10.1038/nature05143 | pmc = 3366509 |bibcode = 2006Natur.443..870S }}</ref>

== 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 protein]]s, RAMP1, RAMP2, or RAMP3.<ref name="Hay">{{cite journal |vauthors=Hay DL, Christopoulos G, Christopoulos A, Sexton PM | title = Amylin receptors: molecular composition and pharmacology | journal = Biochem. Soc. Trans. | volume = 32 | issue = Pt 5 | pages = 865–7 |date=November 2004 | pmid = 15494035 | doi = 10.1042/BST0320865 }}</ref>

==See also==
* [[carboxypeptidase E]]
* [[Pancreatic islets]]
* [[Peptidylglycine alpha-amidating monooxygenase|peptidylglycine alpha-amidating monooxygenase (PAM)]]
* [[Pramlintide]]
* [[Proprotein convertase 1|proprotein convertase 1/3 (PC1/3)]]
* [[proprotein convertase 2]] (PC2)
* [[Diabetes mellitus type 2|Type II Diabetes]]

==References==
{{Reflist|35em}}

==Further reading==
{{refbegin|35em}}
*{{cite journal |vauthors=Westermark P, Andersson A, Westermark GT |title=Is aggregated IAPP a cause of beta-cell failure in transplanted human pancreatic islets? |journal=Curr. Diab. Rep. |volume=5 |issue= 3 |pages= 184–8 |year= 2005 |pmid= 15929864 |doi=10.1007/s11892-005-0007-2 }}
*{{cite journal  |vauthors=Höppener JW, Oosterwijk C, Visser-Vernooy HJ |title=Characterization of the human islet amyloid polypeptide/amylin gene transcripts: identification of a new polyadenylation site |journal=Biochem. Biophys. Res. Commun. |volume=189 |issue= 3 |pages= 1569–77 |year= 1993 |pmid= 1282806 |doi=10.1016/0006-291X(92)90255-J  |display-authors=etal}}
*{{cite journal  |vauthors=Hubbard JA, Martin SR, Chaplin LC |title=Solution structures of calcitonin-gene-related-peptide analogues of calcitonin-gene-related peptide and amylin |journal=Biochem. J. |volume=275 |issue=  Pt 3|pages= 785–8 |year= 1991 |pmid= 2039456 |doi=  | pmc=1150122  |display-authors=etal}}
*{{cite journal  |vauthors=Butler PC, Chou J, Carter WB |title=Effects of meal ingestion on plasma amylin concentration in NIDDM and nondiabetic humans |journal=Diabetes |volume=39 |issue= 6 |pages= 752–6 |year= 1990 |pmid= 2189768 |doi=10.2337/diabetes.39.6.752  |display-authors=etal}}
*{{cite journal  |vauthors=van Mansfeld AD, Mosselman S, Höppener JW |title=Islet amyloid polypeptide: structure and upstream sequences of the IAPP gene in rat and man |journal=Biochim. Biophys. Acta |volume=1087 |issue= 2 |pages= 235–40 |year= 1990 |pmid= 2223885 |doi=  10.1016/0167-4781(90)90210-S|display-authors=etal}}
*{{cite journal  |vauthors=Christmanson L, Rorsman F, Stenman G |title=The human islet amyloid polypeptide (IAPP) gene. Organization, chromosomal localization and functional identification of a promoter region |journal=FEBS Lett. |volume=267 |issue= 1 |pages= 160–6 |year= 1990 |pmid= 2365085 |doi=10.1016/0014-5793(90)80314-9  |display-authors=etal}}
*{{cite journal  |vauthors=Clark A, Edwards CA, Ostle LR |title=Localisation of islet amyloid peptide in lipofuscin bodies and secretory granules of human B-cells and in islets of type-2 diabetic subjects |journal=Cell Tissue Res. |volume=257 |issue= 1 |pages= 179–85 |year= 1989 |pmid= 2546670 |doi=10.1007/BF00221649  |display-authors=etal}}
*{{cite journal  |vauthors=Nishi M, Sanke T, Seino S |title=Human islet amyloid polypeptide gene: complete nucleotide sequence, chromosomal localization, and evolutionary history |journal=Mol. Endocrinol. |volume=3 |issue= 11 |pages= 1775–81 |year= 1990 |pmid= 2608057 |doi=10.1210/mend-3-11-1775  |display-authors=etal}}
*{{cite journal  |vauthors=Mosselman S, Höppener JW, Lips CJ, Jansz HS |title=The complete islet amyloid polypeptide precursor is encoded by two exons |journal=FEBS Lett. |volume=247 |issue= 1 |pages= 154–8 |year= 1989 |pmid= 2651160 |doi=10.1016/0014-5793(89)81260-8  }}
*{{cite journal  |vauthors=Westermark P, Wernstedt C, Wilander E |title=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 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 11 |pages= 3881–5 |year= 1987 |pmid= 3035556 |doi=10.1073/pnas.84.11.3881  | pmc=304980  |display-authors=etal|bibcode = 1987PNAS...84.3881W }}
*{{cite journal  |vauthors=Mosselman S, Höppener JW, Zandberg J |title=Islet amyloid polypeptide: identification and chromosomal localization of the human gene |journal=FEBS Lett. |volume=239 |issue= 2 |pages= 227–32 |year= 1988 |pmid= 3181427 |doi=10.1016/0014-5793(88)80922-0  |display-authors=etal}}
*{{cite journal  |vauthors=Cooper GJ, Willis AC, Clark A |title=Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 23 |pages= 8628–32 |year= 1988 |pmid= 3317417 |doi=10.1073/pnas.84.23.8628  | pmc=299599  |display-authors=etal|bibcode = 1987PNAS...84.8628C }}
*{{cite journal  |vauthors=Westermark P, Wernstedt C, Wilander E, Sletten K |title=A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas |journal=Biochem. Biophys. Res. Commun. |volume=140 |issue= 3 |pages= 827–31 |year= 1986 |pmid= 3535798 |doi=10.1016/0006-291X(86)90708-4  }}
*{{cite journal  |vauthors=Höppener JW, Verbeek JS, de Koning EJ |title=Chronic overproduction of islet amyloid polypeptide/amylin in transgenic mice: lysosomal localization of human islet amyloid polypeptide and lack of marked hyperglycaemia or hyperinsulinaemia |journal=Diabetologia |volume=36 |issue= 12 |pages= 1258–65 |year= 1994 |pmid= 8307253 |doi=10.1007/BF00400803  |display-authors=etal}}
*{{cite journal  |vauthors=Lim YA, Ittner LM, Lim YL, Götz J |title=Human but not rat amylin shares neurotoxic properties with Abeta42 in long-term hippocampal and cortical cultures|journal=FEBS Lett|volume= 582 |issue= 15 |pages= 2188–2194 |year= 2008 |pmid= 18486611 |doi=10.1016/j.febslet.2008.05.006  }}
{{refend}}

== External links ==
* {{MeshName|amylin}}
* {{cite web | url = http://www.pdb.org/pdb/explore.do?structureId=1KUW | title =  Amylin Nucleation Site | format = | work = PDB entry 1KUW | publisher = [[Protein Data Bank|RCSB Protein Data Bank]] | pages = | language = | quote = | accessdate = 2008-05-28| archiveurl= https://web.archive.org/web/20080416113214/http://www.pdb.org/pdb/explore.do?structureId=1KUW| archivedate= 16 April 2008 <!--DASHBot-->| deadurl= no}}
* {{UCSC gene info|DAP}}
* {{UCSC gene info|IAPP}}

{{PDB Gallery|geneid=3375}}
{{Amyloidosis}}
{{Gastrointestinal hormones}}
{{Neuropeptidergics}}

[[Category:Peptide hormones]]
[[Category:Diabetes]]
[[Category:Endocrine system]]
[[Category:Anti-diabetic drugs]]