ライフサイエンスコーパス: IAPP

1 IAPP expression is increased in the context of insulin r

2 IAPP fibrils triggered limited activation of complement

3 IAPP is a basic 37-residue polypeptide responsible for i

4 IAPP is responsible for amyloid formation in patients wi

5 IAPP is secreted in conjunction with insulin from pancre

6 IAPP plays a physiological role in glucose regulation; h

7 IAPP was previously shown to oligomerize cooperatively o

8 IAPP, a 37 amino-acid peptide hormone belonging to the c

9 IAPP-induced activation of TLR2 and secretion of IL-1 ma

10 ture amyloid fibrils made up of Abeta(1-40), IAPP(8-24), or Sup35NM(7-16).

11 he hydrophobic binding sites in Abeta(1-40), IAPP(8-24), or Sup35NM(Ac7-16) Y-->F amyloid fibrils see

12 pressing human IAPP dramatically accelerates IAPP amyloid deposition, which was accompanied by clinic

13 Not all IAPP oligomers are toxic; toxicity depends on their part

14 Abeta and IAPP are representative amyloidoses and are used to high

15 and peptides (alpha-synuclein, Abeta42, and IAPP).

16 ata indicated that cells exposed to C4BP and IAPP in comparison with IAPP alone increased expression

17 ession led to decreased FoxA2 expression and IAPP promoter occupancy and to a significant reduction i

18 Kinetic studies with wild-type IAPP and IAPP mutants demonstrate that membrane leakage is induce

19 expose beta-cells to a burden of insulin and IAPP biosynthetic demand that exceeds the cellular capac

20 Insulin and IAPP were secreted in an approximately 10:1 ratio and di

21 igher-molecular-weight insulin oligomers and IAPP homodimers.

22 al beta-cell signaling pathways of TXNIP and IAPP and thereby provide new mechanistic insight into an

23 ever, so far no connection between TXNIP and IAPP signaling had been reported.

24 (FITC)-labeled IAPP, anti-insulin, and anti-IAPP antibodies in an 8.15 cm mixing channel maintained

25 Islet homogenates immunodepleted with anti-IAPP-specific antibodies were not able to induce IAPP ag

26 , a US Food and Drug Administration-approved IAPP variant all induce membrane leakage, but are not cy

27 ns cannot be the origin of cooperativity, as IAPP and its enantiomer D-IAPP are equally cross-coopera

28 ds in vitro we have investigated whether aS, IAPP, and unprocessed IAPP, pro-IAPP, polypeptides can c

29 nd varying degree of co-localization between IAPP fibrils and C1q, C3d, as well as C4BP and factor H

30 The relationship between IAPP's conformational landscape and its capacity to medi

31 Heterologous seeding between IAPP and Abeta shown here may represent a molecular link

32 hesized that beta-cells produce HS that bind IAPP via regions of highly sulfated disaccharides.

33 rd zinc-free monomers and dimers, which bind IAPP monomers more efficiently compared to zinc-bound he

34 ism data indicate MDPs do not act by binding IAPP monomers.

35 y contribute to amyloid formation by binding IAPP via their heparan sulfate (HS) chains.

36 residues with Ala dramatically impairs both IAPP self-assembly and hetero-assembly with Abeta40(42).

37 lasmid DNA (pDNA) individually produced both IAPP and LEP peptides in vitro and in vivo.

38 The proportion of HS that bound IAPP was similar in both cell lines ( approximately 65%)

39 Islet amyloidosis by IAPP contributes to pancreatic beta-cell death in diabet

40 ormation from IAPP was stimulated equally by IAPP-bound beta-TC3 HS, non-bound beta-TC3 HS, and non-b

41 amidated C-terminus in amyloid formation by IAPP and in stabilizing oligomers is not known.

42 and directly bind misfolded, seeding-capable IAPP species.

43 ecies of aggregating peptides (human and cat IAPP) and two species of non-aggregating peptides (pig a

44 odel anionic membranes are known to catalyze IAPP amyloid formation in vitro.

45 Here, we determined that beta cell IAPP content is regulated by autophagy through p62-depen

46 ulation of pancreatic homogenates containing IAPP aggregates into transgenic mice expressing human IA

47 By contrast, IAPP and proIAPP were detected in cerebral and vascular

48 In contrast, IAPP-bound HS from NMuMG cells contained frequent highly

49 sicle leakage, but the features that control IAPP-membrane interactions and the connection with cellu

50 milarities and major differences controlling IAPP cross-peptide interaction with Abeta40(42) versus i

51 hydrophobic residues within the amyloid core IAPP region as hot spots or key residues of its cross-in

52 cooperativity, as IAPP and its enantiomer D-IAPP are equally cross-cooperative.

53 In type II diabetes, IAPP aggregates in a process that is associated with bet

54 we examined the binding of freshly-dissolved IAPP as well as pre-formed fibrils with two homologous p

55 Soluble IAPP species produced early during IAPP aggregation provided a Toll-like-receptor-2- (TLR2-

56 we define the toxic species produced during IAPP amyloid formation and link their properties to indu

57 the misfolding and aggregation of endogenous IAPP in islet cultures obtained from transgenic mouse or

58 partition into neutral membranes and enhance IAPP misfolding.

59 ical intermediate that, in turn, facilitates IAPP misfolding.

60 BMDMs treated with soluble but not fibrillar IAPP provided a TLR2-dependent priming stimulus for ATP-

61 with LODs of 20 nM for insulin and 1 nM for IAPP.

62 everal features with structures reported for IAPP fibrils and demonstrate the importance of hydrogen

63 ream adaptor protein MyD88 were required for IAPP-induced cytokine production by BMDMs, a process tha

64 (+)CD11b(+)CD11c(+) cells) were required for IAPP-induced mRNA expression of the proinflammatory cyto

65 lymeric C4BP with multiple binding sites for IAPP neutralizes lytic activity of IAPP.

66 have identified a novel TXNIP/miR-124a/FoxA2/IAPP signaling cascade linking the critical beta-cell si

67 aken together, C4BP protects beta-cells from IAPP cytotoxicity by modulating IAPP fibril formation ex

68 matory therapies may protect beta-cells from IAPP-induced islet dysfunction.

69 Fibril formation from IAPP was stimulated equally by IAPP-bound beta-TC3 HS, n

70 been used to monitor oligomer formation from IAPP.

71 Furthermore, IAPP also bound complement inhibitors factor H and C4b-b

72 and microscopy to investigate alpha-helical IAPP-membrane interactions.

73 rtant in determining approaches to reduce HS-IAPP interactions and ultimately prevent islet amyloid f

74 Human IAPP damages anionic membranes, promoting vesicle leakag

75 Human IAPP is potentially toxic, especially as membrane-permea

76 ges of immunogold-labeled rat IAPP and human IAPP show both forms to localize to mitochondrial crista

77 loidogenic rat IAPP is as effective as human IAPP at disrupting standard anionic model membranes unde

78 positive fibrillar amyloid produced by human IAPP aggregation failed to activate TLR2.

79 K mutant inhibits amyloid formation by human IAPP.

80 Transgenic mice with beta-cell human IAPP (hIAPP) expression had impaired glucose tolerance,

81 Furthermore, mice expressing human IAPP but deficient for beta cell autophagy through genet

82 egates into transgenic mice expressing human IAPP dramatically accelerates IAPP amyloid deposition, w

83 tients with T2D and rodents expressing human IAPP.

84 This effect is stronger for human IAPP than for the less toxic rat IAPP.

85 In human IAPP-expressing mice that lack beta cell autophagy, incr

86 ccumulation of toxic IAPP oligomers in human IAPP-expressing murine models.

87 gulation of Il1b and Tnf expression in human IAPP-expressing transgenic mouse islets.

88 proIAPP, or amyloid-beta (Abeta) into human IAPP transgenic mice triggered IAPP amyloid formation in

89 known natural mutation found in mature human IAPP is a Ser20-to-Gly missense mutation, found with sma

90 emizygous for transgenic expression of human IAPP did not develop diabetes; however, loss of beta cel

91 Induction of high levels of human IAPP in mouse beta cells resulted in accumulation of thi

92 P is significantly slower than that of human IAPP in water but not in denaturant, providing experimen

93 ophenylalanine (p-cyanoPhe) variant of human IAPP, show that the designed S20K mutant inhibits amyloi

94 s produced extensive investigations on human IAPP (hIAPP) and its interactions with lipid bilayers.

95 Like other amyloidogenic peptides, human IAPP induces macrophage IL-1beta secretion by stimulatin

96 icity induced by oligomerization-prone human IAPP.

97 structural effects of fragments of the human IAPP and several rat IAPP mutants.

98 attributable to accumulation of toxic human IAPP oligomers and loss of beta cell mass.

99 In an islet culture model where human IAPP (hIAPP) transgenic mouse islets develop amyloid but

100 ted that treatment of INS-1 cells with human IAPP (hIAPP) enhances cell death, inhibits cytoprolifera

101 P-IAPP; a designed double mutant, G24P, I26P-IAPP; a double N-methylated variant; and pramlintide, a

102 A designed point mutant, I26P-IAPP; a designed double mutant, G24P, I26P-IAPP; a doubl

103 by both soluble and fibrillar aggregates in IAPP-induced islet inflammation.

104 to shed light on the role of cholesterol in IAPP aggregation and the related membrane disruption.

105 occupancy and to a significant reduction in IAPP mRNA and protein expression and also effectively in

106 mbrane damage is known to play a key role in IAPP cytotoxicity, and therefore the effects of lipid co

107 se residues in isolation plays a key role in IAPP self-assembly, whereas simultaneous substitution of

108 ys further demonstrated that TXNIP increases IAPP expression at the transcriptional level, and we dis

109 -specific antibodies were not able to induce IAPP aggregation.

110 and also effectively inhibited TXNIP-induced IAPP expression.

111 ncentrations of insulin and Zn(2+) - inhibit IAPP aggregation in healthy individuals.

112 IAPP amyloid formation, whereas they inhibit IAPP amyloid formation.

113 ly target misfolded amyloid seeds to inhibit IAPP misfolding which, along with direct anti-apoptotic

114 fluorescence studies show that HNG inhibits IAPP misfolding at highly substoichiometric concentratio

115 noline docks specifically with intracellular IAPP and rescues beta-cells from toxicity.

116 n, fluorescein isothiocyanate (FITC)-labeled IAPP, anti-insulin, and anti-IAPP antibodies in an 8.15

117 ATP-induced IL-1beta secretion, whereas late IAPP aggregates induced NLRP3-dependent IL-1beta secreti

118 It appears that healthy pancreatic EVs limit IAPP amyloid formation via direct binding as a tissue-sp

119 Here, we examined how misfolded IAPP affects Abeta aggregation and AD pathology in vitro

120 Our underlying hypothesis is that misfolded IAPP produced in T2D potentiates AD pathology by cross-s

121 lthy patients and patients with T2D modulate IAPP amyloid formation.

122 a-cells from IAPP cytotoxicity by modulating IAPP fibril formation extracellularly and also, after up

123 e effects of lipid composition on modulating IAPP-membrane interactions have been the focus of intens

124 Furthermore, addition of monomeric IAPP to a rat insulinoma cell line (INS-1) resulted in d

125 human erythrocytes incubated with monomeric IAPP, whereas no lysis was observed after incubation wit

126 Moreover, IAPP-induced IL-1beta synthesis and caspase-1 activation

127 dogenic hIAPP but not nonamyloidogenic mouse IAPP.

128 designing intervention strategies and novel IAPP analogs for the management of type 2 diabetes, Alzh

129 rmore, our experiments yielded several novel IAPP analogs, whose sequences are highly similar to that

130 Remarkably, we observe IAPP and magainin 2 to be fully cross-cooperative in the

131 Incorporation of residues 11-17 of IAPP (RLANFLV) into a macrocyclic beta-sheet peptide res

132 s of peptides derived from residues 11-17 of IAPP that assemble to form tetramers.

133 er the membrane curvature-sensing ability of IAPP and find that it transitions from inducing to sensi

134 little is known about the mode of action of IAPP amyloid inhibitors, and this has limited rational d

135 id fiber formation, the inhibitory action of IAPP variants, and the competition between ordered and d

136 sites for IAPP neutralizes lytic activity of IAPP.

137 We observed that addition of IAPP seeds accelerates Abeta aggregation in vitro in a s

138 re also induced in vivo by administration of IAPP aggregates prepared in vitro using pure, synthetic

139 ct of cholesterol on the amyloidogenicity of IAPP and help explain its debated role in type 2 diabete

140 a pre-amyloid, alpha-helical conformation of IAPP.

141 enerate the physiologically relevant form of IAPP accelerates amyloid formation, demonstrating that t

142 Here, we report that amyloid formation of IAPP can be strongly inhibited by the extracellular envi

143 activation and may be enhancing formation of IAPP fibrils from cytotoxic oligomers.

144 Furthermore, C4BP enhanced formation of IAPP fibrils in vitro.

145 Aggregation and formation of IAPP-amyloid play a critical role in beta-cell death in

146 Finally, induction of IAPP deposition and diabetic abnormalities were also ind

147 Several known inhibitors of IAPP amyloid formation are shown to be less effective in

148 computationally investigated interactions of IAPP with different insulin oligomers and compared with

149 The kinetics of IAPP amyloid formation are strongly dependent on ionic s

150 l has a negligible effect on the kinetics of IAPP fibril growth on the surface of the bilayer.

151 ought to determine the specific mechanism of IAPP-induced proIL-1beta synthesis.

152 cell transplants, however the mechanisms of IAPP-induced cytotoxicity are not known.

153 In contrast, mixing of IAPP and aS monomers results in coaggregation that is fa

154 e chain makes no steric clashes in models of IAPP amyloid fibers, suggesting that the increased rate

155 Analysis of an H18Q mutant of IAPP shows that the charge state of the N-terminus is an

156 hobic interactions in the oligomerization of IAPP-derived peptides.

157 To verify pathogenicity of IAPP-reactive cells, we sorted KS20 tetramer(+) cells an

158 The sulfation pattern of IAPP-bound versus non-bound HS from beta-TC3 cells was s

159 f salts on the growth phase and lag phase of IAPP amyloid formation are strongly correlated.

160 reactivity, it is clear that the presence of IAPP can accelerate aS amyloid formation.

161 mation, even though the N-terminal region of IAPP is believed to be flexible in the amyloid fibers.

162 which we propose that the functional role of IAPP is carried out by the helix-coil conformation, a st

163 assay was used for colocalization studies of IAPP and Abeta in islet amyloid in type 2 diabetic patie

164 racted from the bilayer by the N-terminus of IAPP, and integrated into amyloid aggregates.

165 hose sequences are highly similar to that of IAPP but have distinct amyloid self- or cross-interactio

166 -end distance of CGRP is larger than that of IAPP.

167 we developed a combinatorial gene therapy of IAPP and LEP, where two genes are inserted into a single

168 erstanding of the fate and transformation of IAPP in vivo, which are expected to have consequential b

169 53-deficient tumours through upregulation of IAPP, the gene that encodes amylin, a 37-amino-acid pept

170 ld lead normally non-aggregating variants of IAPP to form fibrils under conditions where an external

171 upon alpha-helical mediated oligomerization, IAPP acquires cell-penetrating peptide (CPP) properties,

172 revealed distinct effects of Lys and aLac on IAPP amyloid aggregation, fibril remodelling and cytotox

173 e expected to have consequential bearings on IAPP glycemic control and T2D pathology.

174 uitous but the effects of protein binding on IAPP aggregation are largely unknown.

175 e abolished the protective effect of C4BP on IAPP cytotoxicity of INS-1 cells.

176 At pH 5.5, where the net charge on IAPP is higher, the effect of different anions scales wi

177 observed differential effects of proteins on IAPP amyloidosis.

178 ngly competes with EGCG for binding sites on IAPP fibers.

179 Furthermore, inoculation of pancreatic IAPP aggregates into the brains of AD transgenic mice re

180 Here, we show that pancreatic IAPP aggregates can promote the misfolding and aggregati

181 In T2D patients IAPP is found aggregating in the extracellular space of

182 ril formation from the amyloidogenic peptide IAPP is dependent on overall sulfation in HS synthesized

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

184 ptides, including islet amyloid polypeptide (IAPP or amylin).

185 he aggregation of islet amyloid polypeptide (IAPP or amylin).

186 Islet amyloid polypeptide (IAPP) aggregates to form amyloid fibrils in patients wit

187 While islet amyloid polypeptide (IAPP) aggregation is associated with beta-cell death in

188 dergic therapy of islet amyloid polypeptide (IAPP) and leptin (LEP) analogues was once an optimistic

189 Deposition of islet amyloid polypeptide (IAPP) as amyloid is a pathological hallmark of the islet

190 beta-cell peptide islet amyloid polypeptide (IAPP) as its unique amyloidogenic component.

191 Aggregation of islet amyloid polypeptide (IAPP) contributes to beta cell dysfunction in type 2 dia

192 Suppression of islet amyloid polypeptide (IAPP) fibril formation by compound 1 was demonstrated by

193 hat C4BP enhances islet amyloid polypeptide (IAPP) fibril formation in vitro Now we report that polym

194 utes the cause to islet amyloid polypeptide (IAPP) for its deleterious effects on the cell membranes.

195 cs of insulin and islet amyloid polypeptide (IAPP) from islets of Langerhans using a microfluidic sys

196 he aggregation of islet amyloid polypeptide (IAPP) in pancreatic beta cells-is limited.

197 in during AD, and islet amyloid polypeptide (IAPP) in pancreatic islets in T2D.

198 Islet amyloid polypeptide (IAPP) is a 37-amino acid amyloid protein intimately asso

199 Islet amyloid polypeptide (IAPP) is a peptide central to beta-cell pathology in typ

200 Islet amyloid polypeptide (IAPP) is a peptide hormone cosecreted with insulin by pa

201 erestingly, human islet amyloid polypeptide (IAPP) is also induced by glucose, aggregates into insolu

202 loid formation by islet amyloid polypeptide (IAPP) is examined.

203 proteins such as islet amyloid polypeptide (IAPP) is implicated in cell death in amyloidoses.

204 Islet amyloid polypeptide (IAPP) is responsible for amyloid formation in type 2 dia

205 Islet amyloid polypeptide (IAPP) is responsible for cell depletion in the pancreati

206 Islet amyloid polypeptide (IAPP) is synthesized in pancreatic beta-cells and co-sec

207 Human islet amyloid polypeptide (IAPP) is the major component of amyloid deposits found i

208 links exist with islet amyloid polypeptide (IAPP) misfolding, a process central to beta-cell dysfunc

209 Islet amyloid polypeptide (IAPP) or amylin, a 37-amino acid residue peptide, is pro

210 e peptide hormone islet amyloid polypeptide (IAPP) plays a central role in diabetes pathology.

211 _loop) of amylin (islet amyloid polypeptide (IAPP) residues 1-8) forms extremely long and stable non-

212 peptide KS20 from islet amyloid polypeptide (IAPP) to be the target Ag for a highly diabetogenic CD4

213 ggregation of the islet amyloid polypeptide (IAPP) to form fibrils and oligomers is important in the

214 the misfolding of islet amyloid polypeptide (IAPP), a critical pathogenic step in type 2 diabetes mel

215 Aggregation of islet amyloid polypeptide (IAPP), a peptide hormone co-synthesized and co-stored wi

216 he aggregation of islet amyloid polypeptide (IAPP), a peptide which shares sequence similarity with A

217 ones, such as the islet amyloid polypeptide (IAPP), is limited to beta-cells due to tissue-specific e

218 s composed of the islet amyloid polypeptide (IAPP), its role in the disease is unknown.

219 rmed fibrils from islet amyloid polypeptide (IAPP), proIAPP, or amyloid-beta (Abeta) into human IAPP

220 that variants of islet amyloid polypeptide (IAPP), which are non-amyloidogenic in homogeneous soluti

221 loid derived from islet amyloid polypeptide (IAPP), which beta cells coexpress with insulin.

222 dered polypeptide islet amyloid polypeptide (IAPP), which is associated with type 2 diabetes (T2D), w

223 eta) peptides and islet amyloid polypeptide (IAPP), whose misfolding propensities are implicated in A

224 sits derived from islet amyloid polypeptide (IAPP).

225 are comprised of islet amyloid polypeptide (IAPP).

226 sits derived from islet amyloid polypeptide (IAPP).

227 diabetes-related islet amyloid polypeptide (IAPP).

228 n (alpha-Syn) and islet amyloid polypeptide (IAPP).

229 d in T2D, amylin [islet amyloid polypeptide (IAPP)] forms amyloids.

230 Islet amyloid polypeptide (IAPP, amylin) is responsible for amyloid formation in ty

231 nic peptides, the islet amyloid polypeptide (IAPP, the peptide comprising the amyloid aggregates in t

232 CGRP) and amylin (islet amyloid polypeptide, IAPP), two intrinsically disordered proteins of the calc

233 membrane leakage is induced by prefibrillar IAPP species and continues over the course of amyloid fo

234 was observed after incubation with preformed IAPP fibrils.

235 hetero-molecular complex formation prevents IAPP from self-association and subsequent aggregation, r

236 many hours to assemble into amyloids and pro-IAPP aggregates even slower under the same conditions.

237 whether aS, IAPP, and unprocessed IAPP, pro-IAPP, polypeptides can cross-react.

238 ter than either protein alone; moreover, pro-IAPP can incorporate aS monomers into its amyloid fibers

239 We discovered that preformed amyloids of pro-IAPP inhibit, whereas IAPP amyloids promote, aS amyloid

240 Amyloids of aS promote pro-IAPP amyloid formation, whereas they inhibit IAPP amyloi

241 ies of non-aggregating peptides (pig and rat IAPP).

242 However, rat IAPP (rIAPP(1-37)), which differs from hIAPP in only six

243 in vivo EM images of immunogold-labeled rat IAPP and human IAPP show both forms to localize to mitoc

244 icity studies show that nonamyloidogenic rat IAPP is as effective as human IAPP at disrupting standar

245 ome smaller upon treatment with human or rat IAPP.

246 fragments of the human IAPP and several rat IAPP mutants.

247 r for human IAPP than for the less toxic rat IAPP.

248 c model membranes under conditions where rat IAPP does not induce cellular toxicity.

249 pancreatic EVs from healthy patients reduce IAPP amyloid formation by peptide scavenging, but T2D pa

250 -out mice, we now found that TXNIP regulates IAPP expression.

251 Remarkably, IAPP colocalized with amyloid plaques in brain parenchym

252 Non-amyloidogenic rodent IAPP and thioflavin-T-positive fibrillar amyloid produce

253 The S20G-IAPP peptide is toxic to cultured rat INS-1 (transformed

254 Using this technique, we show IAPP fibrillizes without an appreciable buildup of nonfi

255 Soluble IAPP species produced early during IAPP aggregation prov

256 ose regulation; however, in certain species, IAPP can aggregate and this process is linked to beta-ce

257 y of both beta-TC3 and NMuMG HS to stimulate IAPP maximal fibril formation, but desulfated HS from bo

258 d to a greater extent by the highly sulfated IAPP-bound NMuMG HS.

259 ates prepared in vitro using pure, synthetic IAPP.

260 The analysis of this variant argues that IAPP is not under strong evolutionary pressure to reduce

261 We conclude that IAPP and magainin 2 induce membrane leakage and cytotoxi

262 Direct binding assays confirmed that IAPP fibrils interact with globular head domains of comp

263 of 7 mice in each group, demonstrating that IAPP amyloid could be enhanced through homologous and he

264 These data provide the first evidence that IAPP aggregates skew resident islet macrophages toward a

265 We found that IAPP binding with insulin oligomers competes with the fo

266 We found that IAPP is causally involved in this tumour regression and

267 Our analysis indicates that IAPP-polyphenol hydrogen bonds and pi-pi stacking combin

268 Our results suggest that IAPP triggers a broad autoimmune response by CD4 T cells

269 enrichment at the proximal FoxA2 site in the IAPP promoter.

270 nt electrostatic repulsion in a model of the IAPP fibrillar state.

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

272 We conclude that C4BP binds to IAPP thereby limiting complement activation and may be e

273 r the strong, hydrophobic binding of C4BP to IAPP.

274 ontribution of resident islet macrophages to IAPP-induced inflammation and beta-cell dysfunction.

275 ind that this toxic gain of function maps to IAPP's capacity to adopt aggregated membrane-bound alpha

276 imer's disease, or other diseases related to IAPP dysfunction or cross-amyloid interactions.

277 ill accelerated fibril formation relative to IAPP alone.

278 is threshold is crossed, intracellular toxic IAPP membrane permeant oligomers (cylindrins) may form,

279 ts beta cells from the accumulation of toxic IAPP oligomers and suggest that enhancing autophagy may

280 light the distinguishing properties of toxic IAPP oligomers and the common features that they share w

281 normally prevents the accumulation of toxic IAPP oligomers in human IAPP-expressing murine models.

282 l death in diabetes, but the nature of toxic IAPP species remains elusive.

283 To track IAPP-reactive T cells in NOD mice and determine how they

284 nformation for rational drug design to treat IAPP induced beta-cell death.

285 a) into human IAPP transgenic mice triggered IAPP amyloid formation in pancreas in 5 of 7 mice in eac

286 Kinetic studies with wild-type IAPP and IAPP mutants demonstrate that membrane leakage

287 ve at seeding amyloid formation by wild-type IAPP, implying that the fibril structures are similar.

288 that inhibits amyloid formation by wild-type IAPP.

289 Studies with unamidated IAPP have provided evidence for formation of an antipara

290 vestigated whether aS, IAPP, and unprocessed IAPP, pro-IAPP, polypeptides can cross-react.

291 d by stabilization of small molecular weight IAPP off-pathway oligomers by the polyphenols.

292 Whereas IAPP forms amyloids within minutes, aS takes many hours

293 formed amyloids of pro-IAPP inhibit, whereas IAPP amyloids promote, aS amyloid formation.

294 It is not clear whether IAPP present in brain originates from pancreas or is loc

295 up to 7.5 hours, the time frame within which IAPP aggregates in the absence of polyphenols.

296 ifferent insulin oligomers and compared with IAPP homodimer formation.

297 exposed to C4BP and IAPP in comparison with IAPP alone increased expression of genes involved in cho

298 t of INS-1 cells and primary rat islets with IAPP also diminished their ability to secrete insulin up

299 Molecular recognition studies with IAPP and Abeta1-42 employing saturation transfer differe

300 Further, C4BP was internalized together with IAPP into INS-1 cells.