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 is secreted in conjunction with insulin from pancre

3 IAPP plays a physiological role in glucose regulation; h

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

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

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

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

8 to the potential pathogenic effects of Abeta-IAPP hetero-oligomerization and development of IAPP base

9 ed and turn-inducing residue Pro accelerated IAPP self-assembly.

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

11 AGE-IAPP, like normal IAPP, is capable of interacting with s

12 We chemically synthesized glycated IAPP (AGE-IAPP) to mimic the consequence of this hormone peptide i

13 Moreover, AGE-IAPP can induce normal IAPP to expedite its aggregation

14 ar dichroism spectra also indicated that AGE-IAPP exhibited faster conformational changes from random

15 Our data revealed that AGE-IAPP formed amyloid faster than normal IAPP, and higher-

16 normal IAPP, and higher-molecular-weight AGE-IAPP oligomers were also observed in the early stage of

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

32 Humans form islet amyloid, but baboon IAPP has not been studied.

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

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

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

36 y polypeptide human cathelicidin LL-37 binds IAPP with nanomolar affinity and effectively suppresses

37 Instead, HNG binds IAPP near the disordered NFGAIL motif, wedging itself be

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

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

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

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

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

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

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

52 ingly, both insulin and rat sequence delayed IAPP LLPS, which may reflect physiology.

53 his strong attraction, HNG does not denature IAPP.

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 s are the most toxic species produced during IAPP amyloid formation.

58 -enriched regions and related to an elevated IAPP over insulin ratio in the newly generated beta cell

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

60 partition into neutral membranes and enhance IAPP misfolding.

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

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

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

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

65 Asn-21 amide side chain is not required for IAPP nucleation and amyloid elongation, as N21A and N21G

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

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

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

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

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

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

72 been used to monitor oligomer formation from IAPP.

73 We chemically synthesized glycated IAPP (AGE-IAPP) to mimic the consequence of this hormone

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

75 Simulations also indicate that HNG-IAPP heterodimers are 10 times more stable than IAPP hom

76 Human IAPP damages anionic membranes, promoting vesicle leakag

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

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

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

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

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

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

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

84 tients with T2D and rodents expressing human IAPP.

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

86 The baboon peptide differs from human IAPP at three positions containing K1I, H18R, and A25T s

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

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

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

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

91 teins implicated in neurodegeneration, human IAPP (hIAPP) forms membrane permeant toxic oligomers imp

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

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

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

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

96 icity induced by oligomerization-prone human IAPP.

97 We demonstrate that human IAPP undergoes AWI-catalyzed liquid-liquid phase separat

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

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

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

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

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

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

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

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

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

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

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

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

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

111 and also effectively inhibited TXNIP-induced IAPP expression.

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

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

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

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

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

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

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

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

120 e found that HNG does not deconstruct mature IAPP fibrils and oligomers, consistent with the simulati

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

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

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

124 osition 21 as a hinge residue that modulates IAPP amyloidogenicity and cytotoxicity.

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

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

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

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

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

130 dogenic hIAPP but not nonamyloidogenic mouse IAPP.

131 Moreover, AGE-IAPP can induce normal IAPP to expedite its aggregation process, and its fibril

132 AGE-IAPP, like normal IAPP, is capable of interacting with synthetic membranes

133 t AGE-IAPP formed amyloid faster than normal IAPP, and higher-molecular-weight AGE-IAPP oligomers wer

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

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

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

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

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

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

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

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

142 sites for IAPP neutralizes lytic activity of IAPP.

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

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

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

146 itical role in the in vitro self-assembly of IAPP.

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

148 PP hetero-oligomerization and development of IAPP based therapies for AD and T2D.

149 Our findings reveal distinct effects of IAPP peptides in modulating Abeta aggregation and toxici

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

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

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

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

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

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

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

157 ed insights into the molecular mechanisms of IAPP self-assembly and to probe the conformational natur

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

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

160 demonstrated that glycation modification of IAPP promotes the amyloidogenic properties of IAPP, and

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

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

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

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

165 APP promotes the amyloidogenic properties of IAPP, and it may play a role in accumulating additional

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

167 nonconservative substitution in a region of IAPP that is believed to be important for aggregation, b

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

169 he S14G-HN mutant (HNG) and a diverse set of IAPP structures.

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

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

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

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

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

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

176 53-deficient tumours through upregulation of IAPP, the gene that encodes amylin, a 37-amino-acid pept

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

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

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

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

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

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

183 observed differential effects of proteins on IAPP amyloidosis.

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

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

186 fragments reduces the formation of parallel IAPP beta-sheets and subsequent nucleation of mature amy

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

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

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

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

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

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

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

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

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

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

197 l environments in islet amyloid polypeptide (IAPP) fibrils and plaques, which are hallmarks of Type I

198 lypeptide hormone islet amyloid polypeptide (IAPP) forms islet amyloid in type 2 diabetes, a process

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

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

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

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

203 The islet amyloid polypeptide (IAPP) is a 37-residue peptide hormone whose deposition a

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

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

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

207 self-assembly of islet amyloid polypeptide (IAPP) is linked to pancreatic inflammation, beta-cell de

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

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

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

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

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

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

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

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

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

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

218 abetes-associated islet amyloid polypeptide (IAPP), a hydrophobic-hydrophilic interface-dependent pro

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

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

221 sits derived from islet amyloid polypeptide (IAPP), a protein co-expressed with insulin by beta-cells

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

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

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

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

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

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

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

229 sits derived from islet amyloid polypeptide (IAPP).

230 are comprised of islet amyloid polypeptide (IAPP).

231 sits derived from islet amyloid polypeptide (IAPP).

232 diabetes-related islet amyloid polypeptide (IAPP).

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

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

235 tein glycation on islet amyloid polypeptide (IAPP, also known as amylin) aggregation, which was stron

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

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

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

239 was observed after incubation with preformed IAPP fibrils.

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

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

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

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

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

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

246 ecular interactions involving Asn-21 promote IAPP primary nucleation events by modulating the conform

247 fibrils can also act as templates to promote IAPP aggregation.

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

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

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

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

252 Using nonamyloidogenic rat IAPP, we show that, whereas LLPS does not require the am

253 ome smaller upon treatment with human or rat IAPP.

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

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

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

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

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

259 Remarkably, IAPP colocalized with amyloid plaques in brain parenchym

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

261 why the six residue substitutions in rodent IAPP prevent aggregation; and (iv) suggests regions resp

262 Soluble IAPP species produced early during IAPP aggregation prov

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

264 ates prepared in vitro using pure, synthetic IAPP.

265 P heterodimers are 10 times more stable than IAPP homodimers, which explains the substoichiometric ab

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

295 ifferent insulin oligomers and compared with IAPP homodimer formation.

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

297 7 segments that mediate its interaction with IAPP.

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.