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a hydrocarbon radical that occurs in many organic compounds

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/08/09 14:19:20」(JST)

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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.^[3] It is cosecreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1. Amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing 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.^[4]

Synthesis

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.^[4]^[5]

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).^[6] At the C-terminus Carboxypeptidase E then removes the terminal lysine and arginine residues.^[7] 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.^[8] After this the transformation from the precursor protein proIAPP to the biologically active IAPP is complete (IAPP sequence: KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY).^[4]

Regulation

Insulin and IAPP are regulated by similar factors since they share a common regulatory promoter motif.^[9] The IAPP promoter is also activated by stimuli which do not affect insulin, such as tumor necrosis factor alpha^[10] and fatty acids.^[11] 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.^[12] 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.^[13]

Amylin also acts in bone metabolism, along with the related peptides calcitonin and calcitonin gene related peptide.^[12]

Rodent amylin knockouts are known to fail to achieve the normal anorexia following food consumption. Because it is an amidated peptide, like many neuropeptides, it is believed to be responsible for the anorectic effect.

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.^[14]^[15]^[16] It was also demonstrated by solid-state NMR spectroscopy that the fragment 20-29 of the human-amylin fragments membranes.^[17] 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.^[18]^[19] 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.^[20]^[21]

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]}

Clinical significance

ProIAPP has been linked to Type 2 diabetes and the loss of islet β-cells.^[22] 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.^[23] 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.^[23] 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.^[7] 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 granule upon which IAPP can accumulate and form amyloid.^[24]

The amyloid formation might be a major mediator of apoptosis, or programmed cell death, in the islet β-cells.^[24] 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.^[23] 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,^[25] 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 apoptotic cell-death in insulin-producing beta cells, an effect that may be relevant to the development of type 2 diabetes.^[26]

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.^[27] 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.^[28] 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.^[29]

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.^[30]

Amylin is degraded in part by insulin-degrading enzyme.^[31]

Receptors

There appear to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3.^[32]

References

^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ "Entrez Gene: IAPP islet amyloid polypeptide".
^ ^a ^b ^c Higham CE, Hull RL, Lawrie L, Shennan KI, Morris JF, Birch NP, Docherty K, Clark A (August 2000). "Processing of synthetic pro-islet amyloid polypeptide (proIAPP) 'amylin' by recombinant prohormone convertase enzymes, PC2 and PC3, in vitro". Eur. J. Biochem. 267 (16): 4998–5004. PMID 10931181. doi:10.1046/j.1432-1327.2000.01548.x.
^ "islet amyloid polypeptide precursor [Homo sapiens]". NCBI. (the current NCBI RefSeq)
^ Sanke T, Bell GI, Sample C, Rubenstein AH, Steiner DF (November 1988). "An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing". J. Biol. Chem. 263 (33): 17243–6. PMID 3053705.
^ ^a ^b Marzban L, Soukhatcheva G, Verchere CB (April 2005). "Role of carboxypeptidase E in processing of pro-islet amyloid polypeptide in {beta}-cells". Endocrinology. 146 (4): 1808–17. PMID 15618358. doi:10.1210/en.2004-1175.
^ ^a ^b ^c Roberts AN, Leighton B, Todd JA, Cockburn D, Schofield PN, Sutton R, Holt S, Boyd Y, Day AJ, Foot EA (December 1989). "Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus". Proc. Natl. Acad. Sci. U.S.A. 86 (24): 9662–6. Bibcode:1989PNAS...86.9662R. PMC 298561 . PMID 2690069. doi:10.1073/pnas.86.24.9662.
^ Höppener JW, Ahrén B, Lips CJ (August 2000). "Islet amyloid and type 2 diabetes mellitus". N. Engl. J. Med. 343 (6): 411–9. PMID 10933741. doi:10.1056/NEJM200008103430607.
^ Cai K, Qi D, Wang O, Chen J, Liu X, Deng B, Qian L, Liu X, Le Y (March 2011). "TNF-α acutely upregulates amylin expression in murine pancreatic beta cells". Diabetologia. 54 (3): 617–26. PMID 21116608. doi:10.1007/s00125-010-1972-9.
^ Qi D, Cai K, Wang O, Li Z, Chen J, Deng B, Qian L, Le Y (January 2010). "Fatty acids induce amylin expression and secretion by pancreatic beta-cells". Am. J. Physiol. Endocrinol. Metab. 298 (1): E99–E107. PMID 19843871. doi:10.1152/ajpendo.00242.2009.
^ ^a ^b Pittner RA, Albrandt K, Beaumont K, Gaeta LS, Koda JE, Moore CX, Rittenhouse J, Rink TJ (1994). "Molecular physiology of amylin". J. Cell. Biochem. 55 Suppl: 19–28. PMID 7929615. doi:10.1002/jcb.240550004.
^ Ratner RE, Dickey R, Fineman M, Maggs DG, Shen L, Strobel SA, Weyer C, Kolterman OG (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". Diabet Med. 21 (11): 1204–12. PMID 15498087. doi:10.1111/j.1464-5491.2004.01319.x.
^ 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". J. Am. Chem. Soc. 130 (20): 6424–9. PMID 18444645. doi:10.1021/ja710484d.
^ 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): 12680–8. PMC 2645932 . PMID 18989933. doi:10.1021/bi801427c.
^ 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): 12689–97. PMC 2953382 . PMID 18989932. doi:10.1021/bi8014357.
^ 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". Biochim. Biophys. Acta. 1768 (9): 2026–9. PMC 2042489 . PMID 17662957. doi:10.1016/j.bbamem.2007.07.001.
^ Palmieri, Leonardo C; Melo-Ferreira, Bruno; Braga, Carolina A; Fontes, Giselle N; Mattos, Luana J; Lima, Luis Mauricio (2013). "Stepwise oligomerization of murine amylin and assembly of amyloid fibrils". Bioph Chem. 181: 135–144. PMID 23974296. doi:10.1016/j.bpc.2013.07.013.
^ 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 (2016). "Regulation of the assembly and amyloid aggregation of murine amylin by zinc". Biophys. Chem. 218: 58–70. PMID 27693831. doi:10.1016/j.bpc.2016.09.008.
^ Cooper GJ, Willis AC, Clark A, Turner RC, Sim RB, Reid KB (1987). "Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients". Proc Natl Acad Sci USA. 84 (23): 8628–32. Bibcode:1987PNAS...84.8628C. PMC 299599 . PMID 3317417. doi:10.1073/pnas.84.23.8628.
^ Westermark P, Wernstedt C, Wilander E, Hayden DW, O'Brien TD, Johnson KH (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". Proc Natl Acad Sci USA. 84 (11): 3881–3885. Bibcode:1987PNAS...84.3881W. PMC 304980 . PMID 3035556. doi:10.1073/pnas.84.11.3881.
^ Paulsson JF, Westermark GT (July 2005). "Aberrant processing of human proislet amyloid polypeptide results in increased amyloid formation". Diabetes. 54 (7): 2117–25. PMID 15983213. doi:10.2337/diabetes.54.7.2117.
^ ^a ^b ^c 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): 2192–201. PMID 16873681. doi:10.2337/db05-1566.
^ ^a ^b 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): 1237–46. PMID 16570161. doi:10.1007/s00125-006-0206-7.
^ Hayden MR (September 2002). "Islet amyloid, metabolic syndrome, and the natural progressive history of type 2 diabetes mellitus". JOP. 3 (5): 126–38. PMID 12221327.
^ 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): 756–60. Bibcode:1994Natur.368..756L. PMID 8152488. doi:10.1038/368756a0.
^ Roth JD, Roland BL, Cole RL, Trevaskis JL, Weyer C, Koda JE, Anderson CM, Parkes DG, Baron AD (May 2008). "Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies". Proc. Natl. Acad. Sci. U.S.A. 105 (20): 7257–62. Bibcode:2008PNAS..105.7257R. PMC 2438237 . PMID 18458326. doi:10.1073/pnas.0706473105.
^ Darce, Keith. "Amylin halts trial of weight-loss therapy".
^ Lim YA, Rhein V, Baysang G, Meier F, Poljak A, Raftery MJ, Guilhaus M, Ittner LM, Eckert A, Götz J (April 2010). "Abeta and human amylin share a common toxicity pathway via mitochondrial dysfunction". Proteomics. 10 (8): 1621–33. PMID 20186753. doi:10.1002/pmic.200900651.
^ "SYMLIN (pramlintide acetate)". Amylin Pharmaceuticals, Inc. 2006. Archived from the original on 13 June 2008. Retrieved 2008-05-28.
^ Shen Y, Joachimiak A, Rosner MR, Tang WJ (October 2006). "Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism". Nature. 443 (7113): 870–4. Bibcode:2006Natur.443..870S. PMC 3366509 . PMID 17051221. doi:10.1038/nature05143.
^ Hay DL, Christopoulos G, Christopoulos A, Sexton PM (November 2004). "Amylin receptors: molecular composition and pharmacology". Biochem. Soc. Trans. 32 (Pt 5): 865–7. PMID 15494035. doi:10.1042/BST0320865.

External links

amylin at the US National Library of Medicine Medical Subject Headings (MeSH)
"Amylin Nucleation Site". PDB entry 1KUW. RCSB Protein Data Bank. Archived 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.

UpToDate Contents

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1. 糖尿病の治療のためのアミリン類似体 amylin analogs for the treatment of diabetes mellitus
2. 2型糖尿病治療のためのGlucagon-like peptide-1受容体拮抗剤 glucagon like peptide 1 receptor agonists for the treatment of type 2 diabetes mellitus
3. 2型糖尿病における持続性高血糖のマネージメント management of persistent hyperglycemia in type 2 diabetes mellitus
4. 成人の1型糖尿病における血糖値マネージメント management of blood glucose in adults with type 1 diabetes mellitus
5. 2型糖尿病の病因 pathogenesis of type 2 diabetes mellitus

English Journal

The effects of organic solvents on the membrane-induced fibrillation of human islet amyloid polypeptide and on the inhibition of the fibrillation.

Wang L1, Li Y1, Lu T1, Li F2.
Biochimica et biophysica acta.Biochim Biophys Acta.2014 Dec;1838(12):3162-70. doi: 10.1016/j.bbamem.2014.09.002. Epub 2014 Sep 10.
The organic solvent dimethylsulphoxide (DMSO) and 1,1,1,3,3,3-hexafluoro-2-isopropanol (HFIP) have been widely used as a pre-treating agent of amyloid peptides and as a vehicle for water-insoluble inhibitors. These solvents are left in many cases as a trace quantity in bulk and membrane environments
PMID 25218343

Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes.

Rafacho A1, Ortsäter H2, Nadal A2, Quesada I1.
The Journal of endocrinology.J Endocrinol.2014 Dec;223(3):R49-R62. Epub 2014 Sep 30.
Glucocorticoids (GCs) are broadly prescribed for numerous pathological conditions because of their anti-inflammatory, antiallergic and immunosuppressive effects, among other actions. Nevertheless, GCs can produce undesired diabetogenic side effects through interactions with the regulation of glucose
PMID 25271217

Convergent chemoenzymatic synthesis of a library of glycosylated analogues of pramlintide: structure-activity relationships for amylin receptor agonism.

Kowalczyk R1, Brimble MA, Tomabechi Y, Fairbanks AJ, Fletcher M, Hay DL.
Organic & biomolecular chemistry.Org Biomol Chem.2014 Nov 7;12(41):8142-51. doi: 10.1039/c4ob01208a. Epub 2014 Jul 17.
Pramlintide (Symlin®), a synthetic analogue of the naturally occurring pancreatic hormone amylin, is currently used with insulin in adjunctive therapy for type 1 and type 2 diabetes mellitus. Herein we report a systematic study into the effect that N-glycosylation of pramlintide has on activation o
PMID 25030939

Japanese Journal

アミリンアナログ・レプチンアナログ(pramlintide・metreleptin)併用療法 (新臨床糖尿病学(上)糖尿病学の最新動向) -- (糖尿病の予防・管理・治療)

古田浩人
日本臨床 70(-), 740-745, 2012-05
NAID 40019325457

膵β細胞機能にかかわるIAPP(アミリン)の役割 (最新臨床糖尿病学(上)糖尿病学の最新動向) -- (糖尿病研究の進歩)

三家登喜夫,森田修平,坂頭節哉
日本臨床 70(-), 134-138, 2012-05
NAID 40019323673

膵ラ氏島アミロイド蛋白(アミリン)と蛋白分解

森田修平,三家登喜夫
内分泌・糖尿病・代謝内科 33(4), 352-357, 2011-10
NAID 40019080688

Related Pictures

★リンクテーブル★

リンク元

「アミリン」

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 ontology
Molecular function	• receptor binding; • hormone activity; • identical protein binding;
Cellular component	• extracellular region; • neuronal cell body; • extracellular space; • inclusion body;
Biological process	• cellular protein metabolic 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 proliferation; • protein destabilization; • protein homooligomerization; • amyloid fibril formation;
	Sources:Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	3375
	15874
	ENSG00000121351
	ENSMUSG00000041681
	P10997
	P12968
	NM_000415; NM_001329201
	NM_010491
	NP_000406; NP_001316130
	NP_034621
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

英: amylin
同: 膵島アミロイドポリペプチド isletamyloid polypeptide IAPP

[1] "Human PubMed Reference:".

[2] "Mouse PubMed Reference:".

[3] "Entrez Gene: IAPP islet amyloid polypeptide".

[Higham-4] Higham CE, Hull RL, Lawrie L, Shennan KI, Morris JF, Birch NP, Docherty K, Clark A (August 2000). "Processing of synthetic pro-islet amyloid polypeptide (proIAPP) 'amylin' by recombinant prohormone convertase enzymes, PC2 and PC3, in vitro". Eur. J. Biochem. 267 (16): 4998–5004. PMID 10931181. doi:10.1046/j.1432-1327.2000.01548.x.

[5] "islet amyloid polypeptide precursor [Homo sapiens]". NCBI. (the current NCBI RefSeq)

[Sanke1988-6] Sanke T, Bell GI, Sample C, Rubenstein AH, Steiner DF (November 1988). "An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing". J. Biol. Chem. 263 (33): 17243–6. PMID 3053705.

[Marzban2005-7] Marzban L, Soukhatcheva G, Verchere CB (April 2005). "Role of carboxypeptidase E in processing of pro-islet amyloid polypeptide in {beta}-cells". Endocrinology. 146 (4): 1808–17. PMID 15618358. doi:10.1210/en.2004-1175.

[Roberts1989-8] Roberts AN, Leighton B, Todd JA, Cockburn D, Schofield PN, Sutton R, Holt S, Boyd Y, Day AJ, Foot EA (December 1989). "Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus". Proc. Natl. Acad. Sci. U.S.A. 86 (24): 9662–6. Bibcode:1989PNAS...86.9662R. PMC 298561 . PMID 2690069. doi:10.1073/pnas.86.24.9662.

[pmid10933741-9] Höppener JW, Ahrén B, Lips CJ (August 2000). "Islet amyloid and type 2 diabetes mellitus". N. Engl. J. Med. 343 (6): 411–9. PMID 10933741. doi:10.1056/NEJM200008103430607.

[pmid21116608-10] Cai K, Qi D, Wang O, Chen J, Liu X, Deng B, Qian L, Liu X, Le Y (March 2011). "TNF-α acutely upregulates amylin expression in murine pancreatic beta cells". Diabetologia. 54 (3): 617–26. PMID 21116608. doi:10.1007/s00125-010-1972-9.

[pmid19843871-11] Qi D, Cai K, Wang O, Li Z, Chen J, Deng B, Qian L, Le Y (January 2010). "Fatty acids induce amylin expression and secretion by pancreatic beta-cells". Am. J. Physiol. Endocrinol. Metab. 298 (1): E99–E107. PMID 19843871. doi:10.1152/ajpendo.00242.2009.

[Pittner_1994-12] Pittner RA, Albrandt K, Beaumont K, Gaeta LS, Koda JE, Moore CX, Rittenhouse J, Rink TJ (1994). "Molecular physiology of amylin". J. Cell. Biochem. 55 Suppl: 19–28. PMID 7929615. doi:10.1002/jcb.240550004.

[Ratner-13] Ratner RE, Dickey R, Fineman M, Maggs DG, Shen L, Strobel SA, Weyer C, Kolterman OG (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". Diabet Med. 21 (11): 1204–12. PMID 15498087. doi:10.1111/j.1464-5491.2004.01319.x.

[pmid18444645-14] 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". J. Am. Chem. Soc. 130 (20): 6424–9. PMID 18444645. doi:10.1021/ja710484d.

[pmid18989933-15] 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): 12680–8. PMC 2645932 . PMID 18989933. doi:10.1021/bi801427c.

[pmid18989932-16] 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): 12689–97. PMC 2953382 . PMID 18989932. doi:10.1021/bi8014357.

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