ライフサイエンスコーパス: amylin

1 gation of islet amyloid polypeptide (IAPP or amylin).

2 including islet amyloid polypeptide (IAPP or amylin).

3 type 2 diabetes) with a known inhibitor (rat amylin).

4 mposed of islet amyloid polypeptide (IAPP or amylin).

5 may respond to a combination of leptin plus amylin.

6 f peptides that require RAMPs; CGRP, AM, and amylin.

7 of-action mediating the anorectic effects of amylin.

8 association with the -HSSNN- residues of the amylin.

9 of a replacement in the N-terminal region of amylin.

10 uggest novel (to our knowledge) findings for amylin.

11 shares three proline substitutions with rat amylin.

12 able to seed amyloid formation by unmodified amylin.

13 n (HDL), leptin, pancreatic polypeptide, and amylin.

14 ificantly more effective inhibitors than rat amylin.

15 due to similarities between Abeta and human amylin.

16 s of chronic overexpression of non-cytotoxic amylin.

17 ats, and in AKO rats infused with aggregated amylin.

18 Amylin (1-30 ng) was administered with the mu-OR agonist

19 ession of these genes yields a high-affinity amylin-1 receptor (AMY1-R)], with highest overlap in the

20 AE, restored their therapeutic efficacy when Amylin 28-33 was administered.

21 Islet amyloid polypeptide (IAPP) or amylin, a 37-amino acid residue peptide, is produced in

22 upregulation of IAPP, the gene that encodes amylin, a 37-amino-acid peptide co-secreted with insulin

23 at overexpress [(25, 28, 29) triprolyl]human amylin, a non-amyloidogenic variant of amylin, designate

24 s expressing the same level of wild-type rat amylin, a nonamyloidogenic isoform, exhibited normal hea

25 The ability of amylin, a pancreatic beta-cell-derived neuropeptide, to

26 Amylin, a pancreatic hormone and neuropeptide, acts prin

27 Amylin, a pancreatic peptide, and amyloid-beta peptides

28 beta]) and amyloid, as well as extracellular amylin, Abeta, and amyloid, was compared between mock- a

29 No differences in extracellular amylin, Abeta40, or Abeta42 were detected, yet only supe

30 irculating levels of amylin may also lead to amylin accumulation and proteotoxicity in peripheral org

31 Amylin accumulation in the brain of diabetic patients wi

32 However, amylin accumulation leads to amyloid formation independe

33 , spongiform change, and capillaries bent at amylin accumulation sites.

34 is included genes such as c-Fos (a marker of amylin activation); Socs3 (a leptin inhibitor); and Cart

35 Amylin acts acutely via the area postrema to reduce food

36 Amylin acts in the CNS to reduce feeding and body weight

37 We postulated that amylin acts in the lateral dorsal tegmental nucleus (LDT

38 ures, but it is not known whether pancreatic amylin affects amyloid pathogenesis in the AD brain.

39 supernatant from VZV-infected cells induced amylin aggregation and, to a lesser extent, Abeta42 aggr

40 e inhibitory effect of the copper(II) ion on amylin aggregation has been recently discovered, but det

41 nent of eukaryotic cells membranes, controls amylin aggregation on model membranes.

42 tructure but can still act as a template for amylin aggregation.

43 let amyloid polypeptide (IAPP, also known as amylin) aggregation, which was strongly associated with

44 Intra-AcbSh amylin alone (3-30 ng) modestly suppressed 10% sucrose i

45 Human amylin (also known as islet amyloid polypeptide/hIAPP) i

46 Human Amylin, also known as human islet amyloid polypeptide (h

47 CTR-like receptor (CLR) for calcitonin (CT), amylin (Amy), calcitonin gene-related peptide (CGRP), an

48 Amylin amyloid formation in the wall of cerebral blood v

49 disorders and aging promote accumulation of amylin amyloid in the cerebrovascular system and gray ma

50 ion of intracellular amyloidogenic proteins (amylin, amyloid precursor protein [APP], and amyloid-bet

51 Amylin amyloids are generally considered a pancreatic di

52 human islet amyloid polypeptide (hIAPP, aka amylin), an amyloidogenic peptide associated with beta-c

53 e 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin

54 atic tissue of subjects with AD, and whether amylin, an amyloidogenic protein deposited in the pancre

55 ssive effects of a peripherally administered amylin analog, suggesting that amylin receptor signaling

56 th diabetes with insulin and pramlintide (an amylin analogue) is more effective than treatment with i

57 unstable and have to be injected separately, amylin analogues are only used by 1.5% of people with di

58 lanation for a positive relationship between amylin and Abeta in blood.

59 asma samples, a positive association between amylin and Abeta1-42 as well as Abeta1-40 is found only

60 eptides assembled into fibrils and catalyzed amylin and Abeta42 aggregation.

61 Mixed amylin and amyloid beta (Abeta) deposits were occasional

62 AKO rats of human amylin, or combined human amylin and apolipoprotein E4, showed that amylin binds t

63 f appetite induced by the anorectic hormones amylin and cholecystokinin, as well as by lithium chlori

64 Furthermore, the amylin and GLP-1 analogs salmon calcitonin (sCT) and lir

65 In chow-maintained rats, systemic amylin and GLP-1 combine to reduce meal size.

66 insulin and leptin levels and an increase in amylin and GLP-1 levels relative to controls.

67 mouse models, we investigated the effects of amylin and its clinical analog, pramlintide, on AD patho

68 efficient inhibition of amyloid formation of Amylin and its disruption by a novel class of conformati

69 Both amylin and its precursor can aggregate and produce toxic

70 ctures of amyloid fibrils of wild-type human amylin and its S20G variant.

71 This study investigates the effect of amylin and pramlintide on Abeta pathogenesis and the pre

72 Both amylin and pramlintide treatments increase the concentra

73 Increased brain Abeta burden by amylin and pramlintide was associated with synaptic loss

74 Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Al

75 erbated the brain accumulation of aggregated amylin and vascular pathology in HIP rats.

76 was observed for rs73069071 within the IAPP (amylin) and SLCO1A2 genes (P=6.2 x 10(-8)).

77 egments from Alzheimer's amyloid-beta, human amylin, and calcitonin.

78 d normal mice injected with aggregated human amylin, and developed in vitro cell models.

79 has been shown to affect levels of insulin, amylin, and glucagon in vivo.

80 ct was associated with higher serum insulin, amylin, and glucagon-like peptide 1 levels compared with

81 t session, plasma levels of insulin, leptin, amylin, and glucagon-like peptide-1 (GLP-1) were assesse

82 dogenous kinetics of co-secreted insulin and amylin, and holds promise as a dual-hormone replacement

83 cortisolaemia; decreases in leptin, insulin, amylin, and incretins; and increases in ghrelin, peptide

84 nificant changes in ghrelin, PP, PYY, GLP-1, amylin, and leptin levels.

85 fasting and postprandial levels of ghrelin, amylin, and leptin were observed.

86 a glucagon-like peptide-1 receptor agonist), amylin, and mechanical distension of the stomach.

87 monoacylglycerol, spermidine, amyloid-beta, amylin, and osmotic shock.

88 lyzes bioactive peptides, including insulin, amylin, and the amyloid beta peptides.

89 Here, we investigated whether amylin- and glucagon-like-peptide-1 (GLP-1)-based combin

90 ck-infected qHA-sps, contained intracellular amylin, APP, and/or Abeta, and amyloid.

91 et amyloid polypeptide (hIAPP, also known as amylin) as islet amyloid is a characteristic feature of

92 Rat amylin, which differs from human amylin at six residues, does not lead to formation of am

93 jury, generating reactive aldehydes, forming amylin-based adducts with reactive aldehydes, and increa

94 However, despite amylin binding throughout the brain, the possible role o

95 the densest concentrations of high-affinity amylin binding; nevertheless, these receptors have not b

96 an amylin and apolipoprotein E4, showed that amylin binds to plasma apolipoproteins.

97 At 24 h after mixing, rat amylin blocks neither beta-sheet and forms its own beta-

98 nal beta-sheet, but at 8 h after mixing, rat amylin blocks the N-terminal beta-sheet instead.

99 ose that detection and disruption of cardiac amylin buildup may be both a predictor of heart dysfunct

100 Preamyloid oligomers formed by baboon amylin, but not baboon amylin fibers, are toxic to cultu

101 s show a significant physiological impact of amylin/calcitonin signaling in CTR-POMC neurons on energ

102 bjects, providing histological evidence that amylin can interact with Abeta and tau in both the pancr

103 ncreases feeding following administration of amylin, CCK, and LiCl, but not LPS.

104 overcome the appetite suppressing effects of amylin, CCK, and LiCl, but not LPS.

105 ay play a role in regulating Abeta in brain, amylin class peptides may provide a new avenue for both

106 DE may be more important in helping regulate amylin clearance.

107 tate, and the dissociation constant of human amylin-copper(II) complex.

108 Using LAESI-IMS-MS for the assessment of amylin-copper(II) interactions demonstrates the utility

109 positively charged surface of the fibrillar amylin cross-beta structure.

110 or eight-saccharide monomers protect against amylin cytotoxicity toward a MIN6 mouse cell model of pa

111 itively charged N-terminal half of monomeric amylin depends on the concentration of negatively charge

112 mmon in individuals with prediabetes, causes amylin deposition and proteotoxicity in pancreatic islet

113 INTERPRETATION: These data identify vascular amylin deposition as a trigger of brain endothelial dysf

114 Amylin deposition in brain blood vessels is associated w

115 We compared amylin deposition in failing and nonfailing hearts from

116 Hyperamylinemia promotes amylin deposition in the heart, causing alterations of c

117 are consistent with the pathological role of amylin deposition in the pancreas, uncover a novel contr

118 It is not known whether vascular amylin deposition is a consequence or a trigger of vascu

119 We found that amylin deposition negatively affects cardiac myocytes by

120 Vascular amylin deposition provokes loss of endothelial cell cove

121 Intriguingly, amylin deposition was also detected in blood vessels and

122 In addition, extensive amylin deposition was found in blood vessels and perivas

123 We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microv

124 Recent studies also identified amylin deposits in failing hearts from patients with obe

125 Furthermore, we found amylin deposits in the brain of these subjects, providin

126 inclusions in pancreatic beta cells, and of amylin deposits in the brain, provides new evidence of a

127 human amylin, a non-amyloidogenic variant of amylin, designated the Line 44 model.

128 In the absence of copper(II), amylin dimers were detected with collision cross section

129 Amylin dose-dependently reversed DAMGO-induced hyperphag

130 disruption, showing the specificity of AcbSh amylin effects to the AMY1-R.

131 We postulated that amylin enhances VMH leptin signaling by inducing interle

132 Amylin exposure for 5 days increased IL-6 mRNA expressio

133 amidation together with structural models of amylin fibers reveals that deamidation in the N-terminal

134 mers formed by baboon amylin, but not baboon amylin fibers, are toxic to cultured beta-cells.

135 Finally, we elucidate the predominant amylin fibrils and assert that native amylin is more sta

136 CreateFibril constructed HET-s, Abeta, and amylin fibrils up to 17 nm in length, and utilized a nov

137 iments indicate that heparin associates with amylin fibrils, rather than enhancing fibrillogenesis ca

138 pathway to the formation of beta-sheet rich amylin fibrils.

139 mylin is postulated to be involved, as human amylin forms amyloid in the pancreases of diabetic patie

140 Baboon amylin forms amyloid on the same timescale as human amyl

141 g reveals that the baboon amylin, like human amylin, forms low-order oligomers in the lag phase of am

142 involved in this tumour regression and that amylin functions through the calcitonin receptor (CalcR)

143 ary evaluation by more than twofold, whereas amylin greater than or equal to 116 pg/ml decreased the

144 The aggregation of human amylin (hA) to form cytotoxic structures has been closel

145 Amylin had no similar effects on cultured astrocytes or

146 ated amyloidogenic systems, human pancreatic amylin (hAM) and alpha-synuclein (alpha-syn), associated

147 Abeta1-42 and human amylin (hAmylin) increase cytosolic cAMP and Ca(2+), tri

148 is non-amyloidogenic, mice expressing human amylin have been developed to investigate this hypothesi

149 ion under the same conditions in which human amylin (hIAPP) forms amyloid fibers.

150 ormed by the amyloidogenic fragment of human amylin hIAPP20-29 subjected to force applied in a variet

151 Aggregates of Amylin hormone, which is co-secreted with insulin from t

152 the recently growing evidence on the role of amylin in AD.

153 rtain whether tau and/or Abeta interact with amylin in either the pancreas or brain of these subjects

154 f heart dysfunction in rats expressing human amylin in pancreatic beta-cells (HIP rats).

155 umulation in the pancreas as well as that of amylin in the brain.

156 hed literature in the areas of incretins and amylin in the management of pediatric diabetes.

157 ttle is known, however, about the effects of amylin in the nucleus accumbens shell (AcbSh), where a c

158 Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (A

159 forms amyloid on the same timescale as human amylin in vitro and exhibits similar toxicity toward cul

160 the abundance and signalling of glucagon and amylin, in addition to that of insulin.

161 infusion of IL-6 antibody also prevented the amylin-induced decrease of body weight gain.

162 Suppression in NAcC DA mediates VTA amylin-induced hypophagia, as combined NAcC D1/D2 recept

163 These results show that amylin-induced VMH microglial IL-6 production is the lik

164 One intracerebroventricular injection of amylin induces a more significant surge in serum Abeta t

165 affecting baseline startle; dorsal striatal amylin infusions had no effect.

166 Intra-AcbSh amylin infusions in rats (0, 30, and 100 ng) reversed am

167 s in the expression of genes involved in the amylin, insulin and leptin signalling pathways within th

168 Aggregation of the peptide hormone amylin into amyloid deposits is a pathological hallmark

169 elf-assembly of the human pancreatic hormone amylin into toxic oligomers and aggregates is linked to

170 Amylin is a calcitonin-related peptide co-secreted with

171 Amylin is a peptide co-secreted with insulin that penetr

172 Amylin is also able to activate ERK signaling specifical

173 d has been established, the S20G mutation in amylin is associated with early-onset T2D.

174 nderpinning T2D, but that amyloidogenesis of amylin is closely involved, we have been seeking to unde

175 Hypersecretion of amylin is common in individuals with prediabetes, causes

176 minant amylin fibrils and assert that native amylin is more stable than its amyloid form.

177 This is striking, because rat amylin is natively disordered and not previously known t

178 As rodent amylin is non-amyloidogenic, mice expressing human amyli

179 The hormone amylin is postulated to be involved, as human amylin for

180 t after September 11, 2001, whereas elevated amylin is protective.

181 Human islet amyloid polypeptide (hIAPP or Amylin) is a 37 residue hormone that is cosecreted with

182 Islet amyloid polypeptide (IAPP or Amylin) is a 37-residue, C-terminally amidated pancreati

183 Human islet amyloid polypeptide (hIAPP or amylin) is a causative agent in pancreatic amyloid depos

184 Islet amyloid polypeptide (IAPP, amylin) is responsible for amyloid formation in type 2 d

185 let amyloid polypeptide (IAPP; also known as amylin) is responsible for islet amyloid formation in ty

186 wledge, that the N-terminal loop (N_loop) of amylin (islet amyloid polypeptide (IAPP) residues 1-8) f

187 c proteins, amyloid beta protein (Abeta) and amylin (islet amyloid polypeptide), respectively.

188 f calcitonin-gene-related peptide (CGRP) and amylin (islet amyloid polypeptide, IAPP), two intrinsica

189 ha-synuclein (aS) forms amyloids and in T2D, amylin [islet amyloid polypeptide (IAPP)] forms amyloids

190 human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with ag

191 Combined amylin+leptin (AMN+LEP) can reduce diet induced obesity

192 SwDI mice brains, and suggest that increased amylin levels or the therapeutic use of pramlintide coul

193 ological conditions that augment insulin and amylin levels, such as oral glucose administration, acut

194 ion with NTE-1 did result in elevated plasma amylin levels, suggesting the in vivo role of IDE action

195 emical cross-linking reveals that the baboon amylin, like human amylin, forms low-order oligomers in

196 -deficient Lep(ob)/Lep(ob) mice were fed the Amylin liver NASH (AMLN) diet for 16 weeks before strati

197 However, elevated circulating levels of amylin may also lead to amylin accumulation and proteoto

198 suggesting the in vivo role of IDE action on amylin may be more significant than an effect on insulin

199 Recent evidence suggests that both Abeta and amylin may express their effects through the amylin rece

200 As naturally occurring amylin may play a role in regulating Abeta in brain, amy

201 We therefore hypothesized that oligomerized amylin might accumulate in the cerebrovascular system an

202 rential association between the beta-hairpin amylin monomer and the metal ion was found.

203 lisional cross sections for human and baboon amylin monomers and dimers, with some differences in the

204 In contrast to oligomers, amylin monomers followed clathrin-dependent endocytosis,

205 Gubra-Amylin NASH (GAN) diet-induced obese (DIO) mice represen

206 dition of water-soluble cholesterol restores amylin oligomer clustering at the PM and internalization

207 nsulin-resistant patients, is known to cause amylin oligomerization and cytotoxicity in pancreatic is

208 oughput screening of potential inhibitors of amylin oligomerization and fibril formation.

209 icroscopy reveals an increased nucleation of amylin oligomers across the plasma membrane in cholester

210 Amylin oligomers and plaques were identified in the temp

211 ransgenic for human amylin, we observed that amylin oligomers attach to the sarcolemma, leading to my

212 ition, sorting, and internalization of toxic amylin oligomers but not monomers in pancreatic rat insu

213 Biochemical studies confirm accumulation of amylin oligomers in the medium after depletion of PM cho

214 Small amylin oligomers were even elevated in nonfailing hearts

215 We found significant accumulation of large amylin oligomers, fibrils, and plaques in failing hearts

216 hanism for selective uptake and clearance of amylin oligomers, impairment of which greatly potentiate

217 skeleton network inhibits internalization of amylin oligomers, which in turn enhances extracellular o

218 nishes cell surface coverage and toxicity of amylin oligomers.

219 es and studied the effects of the aggregated amylin on endothelial cells ex vivo.

220 opamine antagonist-like effects of intra-Acb amylin on feeding and associated behavior.

221 lypeptide, as well as the pancreatic hormone amylin, on energy balance and glycemic control.

222 of supernatant from infected cells to induce amylin or Abeta42 aggregation was quantitated.

223 In conclusion, our findings showed amylin or pramlintide increase Abeta levels and related

224 hirty days of intraperitoneal injection with amylin or pramlintide increased Abeta burden in mice bra

225 l (i.p.) injection of AD animals with either amylin or pramlintide reduces the amyloid burden as well

226 Intravenous infusion in AKO rats of human amylin, or combined human amylin and apolipoprotein E4,

227 not possible to differentiate the effects of amylin overexpression from beta-cell loss in these model

228 differ substantively according to degree of amylin overproduction.

229 de library and identified two short sequence amylin peptides (12-14 aa) that are proteolytically stab

230 -density lipoprotein (LDL), amyloid-beta and amylin peptides, accumulate in such diseases.

231 Eli Lilly and Company and Amylin Pharmaceuticals LLC.

232 logical consequence of cholesterol-regulated amylin polymerization on membranes and biochemical mecha

233 ies: Abeta42, transthyretin, and human islet amylin polypeptide.

234 The pancreatic- and brain-derived hormone amylin promotes negative energy balance and is receiving

235 As amylin readily crosses the blood-brain barrier, our stud

236 cbSh), where a circumscribed zone of intense amylin receptor (AMY-R) binding overlaps reported mappin

237 iating the intake-suppressive effects of VTA amylin receptor (AmyR) activation are unknown.

238 We found that components of the amylin receptor (RAMPs1-3, CTR1a,b) are expressed in cul

239 VTA amylin receptor activation also reduces sucrose self-adm

240 hanisms underlying the hypophagic effects of amylin receptor activation in the LDTg.

241 signaling mediates the hypophagia after LDTg amylin receptor activation.

242 ermogenic reaction to the application of the amylin receptor agonist were observed in male and female

243 These findings suggest that the amylin receptor antagonism may represent a novel therapy

244 Amylin receptor antagonist AC253 blocks increases in int

245 We have previously shown that amylin receptor antagonist, AC253, improves spatial memo

246 nist studies provide novel evidence that VTA amylin receptor blockade increases food intake and atten

247 action analyses to examine expression of the amylin receptor complex in rat LDTg tissue.

248 ain reaction analyses show expression of the amylin receptor complex in the LDTg.

249 We show that mRNA for all components of the amylin receptor complex is expressed in the ventral tegm

250 The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the

251 with stable expression of an isoform of the amylin receptor family, amylin receptor-3 (AMY3).

252 dence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer's disea

253 administered amylin analog, suggesting that amylin receptor signaling in the VTA is physiologically

254 ral knockdown experiments indicate that LDTg amylin receptor signaling is physiologically and potenti

255 amylin may express their effects through the amylin receptor, although the precise mechanisms for thi

256 g in POMC neurons, the core component of the amylin receptor, calcitonin receptor (CTR), was depleted

257 of an isoform of the amylin receptor family, amylin receptor-3 (AMY3).

258 affecting GLP-1 receptor, preproglucagon or amylin-receptor gene expression in the DVC.

259 immunohistochemical data indicate that LDTg amylin receptors are expressed on gamma-aminobutyric aci

260 Activation of LDTg amylin receptors by the agonist salmon calcitonin dose-d

261 Direct activation of VTA amylin receptors reduces the intake of chow and palatabl

262 ing ligand binding properties of CTR and the amylin receptors.

263 : calcitonin gene-related peptide (CGRP) and amylin receptors.

264 reversed DAMGO-induced hyperphagia; 3 ng of amylin reduced DAMGO-mediated feeding by nearly 50%.

265 aggregates and has been widely prescribed in amylin replacement treatment.

266 ization of oligomers from both human and rat amylin (rIAPP) are described.

267 in contrast to hIAPP, non-amyloidogenic rat amylin (rIAPP) reduced oligomer Abeta-mediated neuronal

268 rier, our study demonstrates that peripheral amylin's action on the central nervous system results in

269 er, the neurobiological substrates mediating amylin's effects are not fully characterized.

270 leus with therapeutic potential in mediating amylin's effects on energy balance through gamma-aminobu

271 ormones released following a meal, including amylin, secreted by the pancreas, and cholecystokinin (C

272 Based on its sequence, rat amylin should block formation of the C-terminal beta-she

273 Tissues infiltrated by amylin showed increased interstitial space, vacuolation,

274 g throughout the brain, the possible role of amylin signaling at other nuclei in the control of food

275 r investigation of the physiological role of amylin signaling in POMC neurons, the core component of

276 Here, we investigated whether intra-Acb amylin signaling modulates prepulse inhibition (PPI), a

277 The K1I replacement in human amylin slightly reduces toxicity, whereas the A25T subst

278 expressing endogenous (nonamyloidogenic) rat amylin, studied normal mice injected with aggregated hum

279 nlike the pancreas, there was no evidence of amylin synthesis in the brain.

280 Pramlintide, a synthetic analogue of amylin that is currently used to treat type 1 and type 2

281 Pramlintide is a synthetic analog of human amylin that shares three proline substitutions with rat

282 by human islet amyloid polypeptide (hIAPP or amylin) that is associated with type 2 diabetes.

283 -specific structure for the complex of human amylin (the peptide responsible for islet amyloid format

284 of the human islet amyloid protein (hIAPP or amylin), the protein associated with type II diabetes.

285 tion on the kinetics of amyloid formation by amylin, the causative agent of type 2 diabetes.

286 ntagonist for AMY1-R, blocked the ability of amylin to normalize AMPH-induced PPI disruption, showing

287 ical mechanisms that protect beta-cells from amylin toxicity are poorly understood.

288 llular oligomer accumulation and potentiates amylin toxicity.

289 ers, impairment of which greatly potentiates amylin toxicity.

290 nd microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins

291 In rats, 5 days of amylin treatment decreased body weight gain and/or food

292 Similar 5-day amylin treatment increased VMN leptin-induced phosphoryl

293 production is the likely mechanism by which amylin treatment interacts with VMH leptin signaling to

294 -1beta might function as a sensor of myocyte amylin uptake and a potential mediator of myocyte injury

295 Furthermore, metabolic response to amylin was enhanced in the nestin/hRAMP1 mice whereas th

296 odel of hyperamylinemia transgenic for human amylin, we observed that amylin oligomers attach to the

297 ed but not significantly whereas insulin and amylin were unchanged.

298 ) rats intravenously infused with aggregated amylin were used for in vivo phenotyping.

299 Rat amylin, which differs from human amylin at six residues,

300 We characterized the interaction of amylin with heparin fragments of defined length, which m