Cited by 807Alzheimer's disease research and treatmentsPancreatic function and diabetesPrion Diseases and Protein Misfolding

The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.

Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation.

Open access

Westermark, P, Engström, U, Johnson, K H, Westermark, G T, Betsholtz, C·1990·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.87.13.5036PMC PMC54256

Open this paper in CoChat — free account

Abstract

Islet amyloid polypeptide (IAPP), a putative polypeptide hormone, is a product of pancreatic beta-cells and the major constituent of the amyloid deposits seen mainly in islets of type 2 diabetic humans and diabetic cats. The connection between IAPP amyloid formation and diabetes is unknown, but a limited segment of the IAPP molecule, positions 20-29, seems responsible for the aggregation to fibrils. Differences in the amino acid sequence of this region probably determine whether or not islet amyloid can develop in a particular species. Amyloid fibril formation can be mimicked in vitro with the aid of synthetic peptides. With this technique we show that peptides corresponding to IAPP positions 20-29 of human and cat, species that develop IAPP-derived islet amyloid, form amyloid-like fibrils in vitro. The corresponding IAPP segment from three rodent species that do not develop IAPP-derived amyloid did not give rise to fibrils. Substitution of the human IAPP-(20-29) decapeptide with one or two amino acid residues from species without islet amyloid generally reduced the capacity to form fibrils. We conclude that the sequence Ala-Ile-Leu-Ser-Ser, corresponding to positions 25-29 of human IAPP, is strongly amyloidogenic and that a proline-for-serine substitution in position 28, as in several rodents, almost completely inhibits formation of amyloid fibrils.

Integrity signals

Registry

Crossref · 10.1073/pnas.87.13.5036

Cites

30 of 30 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

The text we found for this paper looks like another document, so its claims and self-check weren’t run. The registry and citation checks still apply.

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The text we found for this paper looks like another document, so the self-check wasn’t run.

Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins
Garnier, J., Osguthorpe, D. J., & Robson, B. (1978) · Journal of Molecular Biology · doi:10.1016/0022-2836(78)90297-8 · Cited by 4,523
Empirical Predictions of Protein Conformation
Chou, P. Y., & Fasman, G. D. (1978) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.47.070178.001343 · Cited by 3,099
Prediction of the Secondary Structure of Proteins from their Amino Acid Sequence
Chou, P. Y., & Fasman, G. D. (1979) · Advances in enzymology and related areas of molecular biology/Advances in enzymology and related subjects · doi:10.1002/9780470122921.ch2 · Cited by 2,917
Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients.
Cooper, G. J., Willis, A. C., Clark, A., Turner, R. C., Sim, R. B., & Reid, K. B. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.23.8628 · Cited by 1,299
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.
Westermark, P., Wernstedt, C., Wilander, E., Hayden, D. W., O'Brien, T. D., & Johnson, K. H. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.11.3881 · Cited by 976
Self-citation
A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas
Westermark, P., Wernstedt, C., Wilander, E., & Sletten, K. (1986) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(86)90708-4 · Cited by 510
Self-citation
Co-localization of islet amyloid polypeptide and insulin in the B cell secretory granules of the human pancreatic islets
Lukinius, A., Wilander, E., Westermark, G. T., Engstr�m, U., & Westermark, P. (1989) · Diabetologia · doi:10.1007/bf00285291 · Cited by 371
Self-citation
Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle.
Cooper, G. J. S., Leighton, B., Dimitriadis, G., Parry‐Billings, M., Kowalchuk, J. M., Howland, K., Rothbard, J. B., Willis, A. C., & Reid, K. B. M. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.20.7763 · Cited by 351
Prediction of chain turns in globular proteins on a hydrophobic basis
Rose, G. D. (1978) · Nature · doi:10.1038/272586a0 · Cited by 329
The influence of amyloid deposits on the islet volume in maturity onset diabetes mellitus
Westermark, P., & Wilander, E. (1978) · Diabetologia · doi:10.1007/bf01219652 · Cited by 291
Self-citation

Show all 30 references

Sorted by citations

β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes
Butler, A. E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R. A., & Butler, P. C. (2003) · Diabetes · doi:10.2337/diabetes.52.1.102 · Cited by 4,011
The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes
Kahn, S. E. (2003) · Diabetologia · doi:10.1007/s00125-002-1009-0 · Cited by 2,166
Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state
Pike, C., Burdick, D., Walencewicz, A., Glabe, C., & Cotman, C. (1993) · The Journal of Neuroscience · doi:10.1523/jneurosci.13-04-01676.1993 · Cited by 1,417
A possible role for π‐stacking in the self‐assembly of amyloid fibrils
Gazit, E. (2002) · The FASEB Journal · doi:10.1096/fj.01-0442hyp · Cited by 1,128
Islet Amyloid Polypeptide, Islet Amyloid, and Diabetes Mellitus
Westermark, P., Andersson, A., & Westermark, G. T. (2011) · Physiological Reviews · doi:10.1152/physrev.00042.2009 · Cited by 1,044
Self-citation
Increased Risk of Type 2 Diabetes in Alzheimer Disease
Janson, J., Laedtke, T., Parisi, J. E., O’Brien, P., Petersen, R. C., & Butler, P. C. (2004) · Diabetes · doi:10.2337/diabetes.53.2.474 · Cited by 950
Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus
Lorenzo, A., Razzaboni, B. L., Weir, G. C., & Yankner, B. A. (1994) · Nature · doi:10.1038/368756a0 · Cited by 820
The Importance of -Cell Failure in the Development and Progression of Type 2 Diabetes
Kahn, S. E. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.9.7713 · Cited by 710
The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles.
Janson, J., Ashley, R. H., Harrison, D. J., McIntyre, S., & Butler, P. C. (1999) · Diabetes · doi:10.2337/diabetes.48.3.491 · Cited by 614
Islet Amyloid in Type 2 Diabetes, and the Toxic Oligomer Hypothesis
Haataja, L., Gurlo, T., Huang, C. J., & Butler, P. C. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0037 · Cited by 624
Islet Amyloid: A Critical Entity in the Pathogenesis of Type 2 Diabetes
Hull, R. L., Westermark, G. T., Westermark, P., & Kahn, S. E. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0405 · Cited by 592
Self-citation
Aggregation and secondary structure of synthetic amyloid βA4 peptides of Alzheimer's disease
Hilbich, C., Kisters–Woike, B., Reed, J., Masters, C. L., & Beyreuther, K. T. (1991) · Journal of Molecular Biology · doi:10.1016/0022-2836(91)90881-6 · Cited by 580
Peptide Conformation and Supramolecular Organization in Amylin Fibrils: Constraints from Solid-State NMR
Luca, S., Yau, W., Leapman, R. D., & Tycko, R. (2007) · Biochemistry · doi:10.1021/bi701427q · Cited by 584
Islet amyloid and type 2 diabetes mellitus.
Höppener, J., Bo, A.-R., & Lips, C. J. M. (2000) · New England Journal of Medicine · doi:10.1056/nejm200008103430607 · Cited by 499
Neuroanatomical Localization, Pharmacological Characterization and Functions of CGRP, Related Peptides and Their Receptors
van Rossum, D., Hanisch, U., & Quirion, R. (1997) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(96)00023-1 · Cited by 517
Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease
Adams, D., Koike, H., Slama, M., & Coelho, T. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0210-4 · Cited by 469
Identification of a penta- and hexapeptide of islet amyloid polypeptide (IAPP) with amyloidogenic and cytotoxic properties.
Tenidis, K., Waldner, M., Bernhagen, J., Fischle, W., Bergmann, M., Weber, M., Merkle, M.-L., Voelter, W., Brunner, H., & Kapurniotu, A. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3422 · Cited by 401
Seeding Specificity in Amyloid Growth Induced by Heterologous Fibrils
O’Nuallain, B., Williams, A. D., Westermark, P., & Wetzel, R. B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311300200 · Cited by 422
Self-citation
Analysis of the Minimal Amyloid-forming Fragment of the Islet Amyloid Polypeptide
Rosenfeld, R., & Gazit, E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102883200 · Cited by 421
Proline and Glycine Control Protein Self-Organization into Elastomeric or Amyloid Fibrils
Rauscher, S., Baud, S., Miao, M., Keeley, F. W., & Pomès, R. (2006) · Structure · doi:10.1016/j.str.2006.09.008 · Cited by 374
A Molecular Model of Alzheimer Amyloid β-Peptide Fibril Formation
Tjernberg, L. O., Callaway, D. J. E., Tjernberg, A., Hahne, S., Lilliehöök, C., Terenius, L. Y., Thyberg, J., & Nordstedt, C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.18.12619 · Cited by 360
Conformational transitions of islet amyloid polypeptide (IAPP) in amyloid formation in Vitro
Kayed, R., Bernhagen, J., Greenfield, N. J., Sweimeh, K., Brunner, H., Voelter, W., & Kapurniotu, A. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2646 · Cited by 351
Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer's disease
Zhao, W.-Q., & Townsend, M. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.10.014 · Cited by 291
Type 2 diabetes as a protein misfolding disease
Mukherjee, A., Morales‐Scheihing, D., Butler, P. C., & Soto, C. A. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.04.005 · Cited by 349
Soluble protein oligomers as emerging toxins in Alzheimer’s and other amyloid diseases
Ferreira, S. T., Vieira, M. N. N., & De Felice, F. G. (2007) · IUBMB Life · doi:10.1080/15216540701283882 · Cited by 335
Watching amyloid fibrils grow by time-lapse atomic force microscopy 1 1Edited by W. Baumeister
Goldsbury, C. S., Kistler, J., Aebi, U., Arvinte, T., & Cooper, G. J. S. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2299 · Cited by 324
Atomic structure of the cross‐β spine of islet amyloid polypeptide (amylin)
Wiltzius, J. J. W., Sievers, S. A., Sawaya, M. R., Cascio, D., Popov, D., Riekel, C., & Eisenberg, D. S. (2008) · Protein Science · doi:10.1110/ps.036509.108 · Cited by 326
Amyloid Fibril Formation from Full-Length and Fragments of Amylin
Goldsbury, C. S., Goldie, K. N., Pellaud, J., Seelig, J., Frey, P., Müller, S. A., Kistler, J., Cooper, G. J. S., & Aebi, U. (2000) · Journal of Structural Biology · doi:10.1006/jsbi.2000.4268 · Cited by 316
Prolines and Aamyloidogenicity in Fragments of the Alzheimer's Peptide .beta./A4
Wood, S. J., Wetzel, R. B., Martin, J. D., & Hurle, M. R. (1995) · Biochemistry · doi:10.1021/bi00003a003 · Cited by 313
Conserved and Cooperative Assembly of Membrane-Bound α-Helical States of Islet Amyloid Polypeptide
Knight, J. D., Hebda, J. A., & Miranker, A. D. (2006) · Biochemistry · doi:10.1021/bi060579z · Cited by 310
Peptides are Building Blocks of Heat-Induced Fibrillar Protein Aggregates of β-Lactoglobulin Formed at pH 2
Akkermans, C., Venema, P., van der Goot, A. J., Gruppen, H., Bakx, E. J., Boom, R. M., & van der Linden, E. (2008) · Biomacromolecules · doi:10.1021/bm7014224 · Cited by 304
Islet amyloid and type 2 diabetes: from molecular misfolding to islet pathophysiology
Jaikaran, E. T. A. S., & Clark, A. (2001) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(01)00078-3 · Cited by 298
Structure–function relationships in peptoids: Recent advances toward deciphering the structural requirements for biological function
Fowler, S. A., & Blackwell, H. E. (2009) · Organic & Biomolecular Chemistry · doi:10.1039/b817980h · Cited by 294
Two-dimensional IR spectroscopy and isotope labeling defines the pathway of amyloid formation with residue-specific resolution
Shim, S., Gupta, R., Ling, Y. L., Strasfeld, D. B., Raleigh, D. P., & Zanni, M. T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805957106 · Cited by 286
Mechanism of IAPP amyloid fibril formation involves an intermediate with a transient β-sheet
Buchanan, L. E., Dunkelberger, E. B., Tran, H. Q., Cheng, P.-N., Chiu, C.-C., Cao, P., Raleigh, D., de Pablo, J. D., Nowick, J., & Zanni, M. (2013) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1314481110 · Cited by 251
Islet amyloid polypeptide: structure, function, and pathophysiology
Akter, R., Cao, P., Noor, H., Ridgway, Z., Tu, L.-H., Wang, H., Wong, A. G., Zhang, X., Abedini, A., Schmidt, A. M., et al. (2016) · Journal of Diabetes Research · doi:10.1155/2016/2798269 · Cited by 273
Diabetes Due to a Progressive Defect in β-Cell Mass in Rats Transgenic for Human Islet Amyloid Polypeptide (HIP Rat)
Butler, A. E., Jang, J., Gurlo, T., Carty, M. D., Soeller, W. C., & Butler, P. C. (2004) · Diabetes · doi:10.2337/diabetes.53.6.1509 · Cited by 267
Chiral Sum Frequency Generation Spectroscopy for Characterizing Protein Secondary Structures at Interfaces
Fu, L., Liu, J., & Yan, E. C. Y. (2011) · Journal of the American Chemical Society · doi:10.1021/ja201575e · Cited by 261
Islet amyloid polypeptide‐induced membrane leakage involves uptake of lipids by forming amyloid fibers
Sparr, E., Engel, M. F. M., Sakharov, D. V., Sprong, M., Jacobs, J., KRUIJFF, B. D., Höppener, J. W. M., & Killian, J. A. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.09.075 · Cited by 257
Thioflavine T interaction with amyloid β-sheet structures
LeVine, H. (1995) · Amyloid · doi:10.3109/13506129509031881 · Cited by 254
Mechanisms of amyloid fibril self‐assembly and inhibition
Gazit, E. (2005) · FEBS Journal · doi:10.1111/j.1742-4658.2005.05022.x · Cited by 248
Amylin Agonists: A Novel Approach in the Treatment of Diabetes
Schmitz, O., Brock, B., & Rungby, J. (2004) · Diabetes · doi:10.2337/diabetes.53.suppl_3.s233 · Cited by 237
Identification of a novel human islet amyloid polypeptide β-sheet domain and factors influencing fibrillogenesis
Jaikaran, E. T. A. S., Higham, C. E., Serpell, L. C., Zurdo, J., Gross, M., Clark, A., & Fraser, P. E. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4593 · Cited by 236
Recent Insights in Islet Amyloid Polypeptide‐Induced Membrane Disruption and Its Role in β‐Cell Death in Type 2 Diabetes Mellitus
Khemtémourian, L., Killian, J. A., Höppener, J. W. M., & Engel, M. F. M. (2008) · Journal of Diabetes Research · doi:10.1155/2008/421287 · Cited by 238
Amyloid Fiber Formation and Membrane Disruption are Separate Processes Localized in Two Distinct Regions of IAPP, the Type-2-Diabetes-Related Peptide
Brender, J., Lee, E. L., Cavitt, M. A., Gafni, A., Steel, D. G., & Ramamoorthy, A. (2008) · Journal of the American Chemical Society · doi:10.1021/ja710484d · Cited by 229
Inhibition of Islet Amyloid Polypeptide Fibril Formation: A Potential Role for Heteroaromatic Interactions
Porat, Y., Mazor, Y., Efrat, S., & Gazit, E. (2004) · Biochemistry · doi:10.1021/bi048582a · Cited by 228
The Interplay of Catalysis and Toxicity by Amyloid Intermediates on Lipid Bilayers: Insights from Type II Diabetes
Hebda, J. A., & Miranker, A. D. (2009) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.050708.133622 · Cited by 223
Advanced Luminescent Materials Based on Organoboron Polymers
Tanaka, K., & Chujo, Y. (2012) · Macromolecular Rapid Communications · doi:10.1002/marc.201200239 · Cited by 223
Human Islet Amyloid Polypeptide Monomers Form Ordered β-hairpins: A Possible Direct Amyloidogenic Precursor
Dupuis, N., Wu, C. F., Shea, J., & Bowers, M. T. (2009) · Journal of the American Chemical Society · doi:10.1021/ja903814q · Cited by 215
Oxidative stress is induced by islet amyloid formation and time-dependently mediates amyloid-induced beta cell apoptosis
Zraika, S., Hull, R. L., Udayasankar, J., Aston‐Mourney, K., Subramanian, S. L., Kisilevsky, R., Szarek, W. A., & Kahn, S. E. (2009) · Diabetologia · doi:10.1007/s00125-008-1255-x · Cited by 215
Direct detection of transient α‐helical states in islet amyloid polypeptide
Williamson, J. A., & Miranker, A. D. (2006) · Protein Science · doi:10.1110/ps.062486907 · Cited by 215
Amyloid β and Amylin Fibrils Induce Increases in Proinflammatory Cytokine and Chemokine Production by THP‐1 Cells and Murine Microglia
Yates, S. L., Burgess, L. H., Kocsis‐Angle, J., Antal, J. M., Dority, M. D., Embury, P. B., Piotrkowski, A. M., & Brunden, K. R. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0741017.x · Cited by 202
Mechanisms of islet amyloidosis toxicity in type 2 diabetes
Abedini, A., & Schmidt, A. M. (2013) · FEBS Letters · doi:10.1016/j.febslet.2013.01.017 · Cited by 206
Islet amyloid polypeptide and type 2 diabetes.
Marzban, L., Park, K., & Verchere, C. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00004-4 · Cited by 191
Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes
Milardi, D., Gazit, E., Radford, S. E., Xu, Y., Gallardo, R. U., Caflisch, A., Westermark, G. T., Westermark, P., Rosa, C. L., & Ramamoorthy, A. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00981 · Cited by 199
Self-citation
Animal Models of Type 2 Diabetes: Clinical Presentation and Pathophysiological Relevance to the Human Condition
Cefalu, W. T. (2006) · ILAR Journal · doi:10.1093/ilar.47.3.186 · Cited by 206
Structural Insights into the Polymorphism of Amyloid-Like Fibrils Formed by Region 20−29 of Amylin Revealed by Solid-State NMR and X-ray Fiber Diffraction
Madine, J., Jack, E. R., Stockley, P. G., Radford, S. E., Serpell, L. C., & Middleton, D. A. (2008) · Journal of the American Chemical Society · doi:10.1021/ja802483d · Cited by 195
Insulin signaling, glucose metabolism and mitochondria: Major players in Alzheimer's disease and diabetes interrelation
Correia, S. C., Santos, R. X., Carvalho, C., Cardoso, S., Candeias, E., Santos, M. S., Oliveira, C. R., & Moreira, P. I. (2012) · Brain Research · doi:10.1016/j.brainres.2011.12.063 · Cited by 202
Short peptide based self-assembled nanostructures: implications in drug delivery and tissue engineering
Panda, J. J., & Chauhan, V. S. (2014) · Polymer Chemistry · doi:10.1039/c4py00173g · Cited by 195
The Parallel Superpleated Beta-structure as a Model for Amyloid Fibrils of Human Amylin
Kajava, A. V., Aebi, U., & Steven, A. C. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.02.029 · Cited by 191
Ion Mobility Spectrometry–Mass Spectrometry Defines the Oligomeric Intermediates in Amylin Amyloid Formation and the Mode of Action of Inhibitors
Young, L. M., Cao, P., Raleigh, D. P., Ashcroft, A. E., & Radford, S. E. (2013) · Journal of the American Chemical Society · doi:10.1021/ja406831n · Cited by 190
Identification and Characterization of a Novel Molecular-recognition and Self-assembly Domain within the Islet Amyloid Polypeptide
Mazor, Y., Gilead, S., Benhar, I., & Gazit, E. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00887-2 · Cited by 186
Helix Stabilization Precedes Aqueous and Bilayer-Catalyzed Fiber Formation in Islet Amyloid Polypeptide
Williamson, J. A., Loria, J. P., & Miranker, A. D. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.07.077 · Cited by 186
Islet amyloid: a complication of islet dysfunction or an aetiological factor in Type 2 diabetes?
Clark, A., & Nilsson, M. R. (2004) · Diabetologia · doi:10.1007/s00125-003-1304-4 · Cited by 191
Structure of α-Helical Membrane-bound Human Islet Amyloid Polypeptide and Its Implications for Membrane-mediated Misfolding
Apostolidou, M., Jayasinghe, S. A., & Langen, R. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801383200 · Cited by 184
Toxic Human Islet Amyloid Polypeptide (h-IAPP) Oligomers Are Intracellular, and Vaccination to Induce Anti-Toxic Oligomer Antibodies Does Not Prevent h-IAPP–Induced β-Cell Apoptosis in h-IAPP Transgenic Mice
Lin, C., Gurlo, T., Kayed, R., Butler, A. E., Haataja, L., Glabe, C. G., & Butler, P. C. (2007) · Diabetes · doi:10.2337/db06-1579 · Cited by 183
Effects of in vivo conditions on amyloid aggregation
Owen, M. C., Gnutt, D., Gao, M., Wärmländer, S. K. T. S., Jarvet, J., Gräslund, A., Winter, R., Ebbinghaus, S., & Strodel, B. (2019) · Chemical Society Reviews · doi:10.1039/c8cs00034d · Cited by 181
In Situ Misfolding of Human Islet Amyloid Polypeptide at Interfaces Probed by Vibrational Sum Frequency Generation
Fu, L., Ma, G., & Yan, E. C. Y. (2010) · Journal of the American Chemical Society · doi:10.1021/ja909546b · Cited by 181
Toxic oligomers and islet beta cell death: guilty by association or convicted by circumstantial evidence?
Zraika, S., Hull, R. L., Verchere, C. B., Clark, A., Potter, K. J., Fraser, P. E., Raleigh, D. P., & Kahn, S. E. (2010) · Diabetologia · doi:10.1007/s00125-010-1671-6 · Cited by 191
Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-β fibrils
Röder, C., Kupreichyk, T., Gremer, L., Schäfer, L. U., Pothula, K. R., Ravelli, R. B. G., Willbold, D., Hoyer, W., & Schröder, G. F. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0442-4 · Cited by 180
Islet amyloid: From fundamental biophysics to mechanisms of cytotoxicity
Cao, P., Marek, P., Noor, H., Patsalo, V., Tu, L., Wang, H., Abedini, A., & Raleigh, D. P. (2013) · FEBS Letters · doi:10.1016/j.febslet.2013.01.046 · Cited by 178
Human IAPP–induced pancreatic β cell toxicity and its regulation by autophagy
Shigihara, N., Fukunaka, A., Hara, A., Komiya, K., Honda, A., Uchida, T., Abe, H., Toyofuku, Y., Tamaki, M., Ogihara, T., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69866 · Cited by 177
Membrane interaction of islet amyloid polypeptide
Jayasinghe, S. A., & Langen, R. (2007) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2007.01.022 · Cited by 181
Structure-based design and study of non-amyloidogenic, double N-methylated IAPP amyloid core sequences as inhibitors of IAPP amyloid formation and cytotoxicity
Kapurniotu, A., Schmauder, A., & Tenidis, K. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5244 · Cited by 173
Islet Amyloid Polypeptide Inserts into Phospholipid Monolayers as Monomer
Engel, M. F. M., Yigittop, H., Elgersma, R. C., Rijkers, D. T. S., Liskamp, R. M. J., KRUIJFF, B. D., Höppener, J. W. M., & Killian, J. A. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.12.020 · Cited by 174
Structures of Rat and Human Islet Amyloid Polypeptide IAPP1−19 in Micelles by NMR Spectroscopy
Nanga, R. P. R., Brender, J., Xu, J., Veglia, G., & Ramamoorthy, A. (2008) · Biochemistry · doi:10.1021/bi8014357 · Cited by 172
The structure and mechanism of formation of human calcitonin fibrils.
Arvinte, T., Cudd, A., & Drake, A. F. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53268-3 · Cited by 172
Islet amyloid deposition limits the viability of human islet grafts but not porcine islet grafts
Potter, K. J., Abedini, A., Marek, P., Klimek-Abercrombie, A. M., Butterworth, S. A., Driscoll, M., Baker, R. L., Nilsson, M. R., Warnock, G. L., Oberholzer, J., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909024107 · Cited by 171
Degradation of Amylin by Insulin-degrading Enzyme
Bennett, R. G., Duckworth, W. C., & Hamel, F. G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m006170200 · Cited by 170
Cu and Zn coordination to amyloid peptides: From fascinating chemistry to debated pathological relevance
Atrián‐Blasco, E., Gonzalez, P., Santoro, A., Aliès, B., Faller, P., & Hureau, C. (2018) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2018.04.007 · Cited by 175
Missense Mutation of Amylin Gene (S20G) in Japanese NIDDM Patients
Sakagashira, S., Sanke, T., Hanabusa, T., Shimomura, H., Ohagi, S., Kumagaye, K. Y., Nakajima, K., & Nanjo, K. (1996) · Diabetes · doi:10.2337/diab.45.9.1279 · Cited by 162
Proinsulin maturation, misfolding, and proteotoxicity
Liu, M. R., Hodish, I., Rhodes, C. J., & Arvan, P. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702697104 · Cited by 159
Atomic Force Microscopy Reveals Defects Within Mica Supported Lipid Bilayers Induced by the Amyloidogenic Human Amylin Peptide
Green, J. D., Kreplak, L., Goldsbury, C. S., Li‐Blatter, X., Stolz, M., Cooper, G. J. S., Seelig, A., Kistler, J., & Aebi, U. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.07.052 · Cited by 161
Time-resolved studies define the nature of toxic IAPP intermediates, providing insight for anti-amyloidosis therapeutics
Abedini, A., Plesner, A., Cao, P., Ridgway, Z. M., Zhang, J., Tu, L., Middleton, C. T., Chao, B., Sartori, D. J., Meng, F., et al. (2016) · eLife · doi:10.7554/elife.12977 · Cited by 160
Extensive islet amyloid formation is induced by development of Type II diabetes mellitus and contributes to its progression: pathogenesis of diabetes in a mouse model
Höppener, J. W. M., Oosterwijk, C., Nieuwenhuis, M. G., Posthuma, G., Thijssen, J. H. H., Vroom, T. M., Ahrén, B., & Lips, C. J. M. (1999) · Diabetologia · doi:10.1007/s001250051175 · Cited by 153
Amyloidogenic peptide oligomer accumulation in autophagy-deficient β cells induces diabetes
Kim, J., Cheon, H., Jeong, Y. T., Quan, W., Kim, K. H., Cho, J. M., Lim, Y.-M., Oh, S. H., Jin, S., Kim, J. H., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69625 · Cited by 159
Amyloidogenesis: historical and modern observations point to heparan sulfate proteoglycans as a major culprit
Ancsin, J. B. (2003) · Amyloid · doi:10.3109/13506120309041728 · Cited by 158
Identifying Structural Features of Fibrillar Islet Amyloid Polypeptide Using Site-directed Spin Labeling
Jayasinghe, S. A., & Langen, R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406853200 · Cited by 153
β-Amyloid-induced changes in cultured astrocytes parallel reactive astrocytosis associated with senile plaques in Alzheimer's disease
Pike, C. J., Cummings, B. J., Monzavi, R., & Cotman, C. W. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90547-9 · Cited by 157
Neuroinflammation and neurologic deficits in diabetes linked to brain accumulation of amylin
Srodulski, S. J., Sharma, S., Bachstetter, A. D., Brelsfoard, J., Pascual, C., Xie, X., Saatman, K. E., Eldik, L. J. V., & Despa, F. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-30 · Cited by 159
Islet Amyloid Polypeptide (IAPP) Transgenic Rodents as Models for Type 2 Diabetes
Matveyenko, A. V., & Butler, P. C. (2006) · ILAR Journal · doi:10.1093/ilar.47.3.225 · Cited by 150
Inhibition of Amyloid Fibril Formation by Peptide Analogues Modified with α‐Aminoisobutyric Acid
Gilead, S., & Gazit, E. (2004) · Angewandte Chemie International Edition · doi:10.1002/anie.200353565 · Cited by 147
Impairment of the Ubiquitin-Proteasome Pathway Is a Downstream Endoplasmic Reticulum Stress Response Induced by Extracellular Human Islet Amyloid Polypeptide and Contributes to Pancreatic β-Cell Apoptosis
Casas, S., Gomis, R., Gribble, F. M., Altirriba, J., Knuutila, S., & Novials, A. (2007) · Diabetes · doi:10.2337/db07-0178 · Cited by 148
Three-Dimensional Structure and Orientation of Rat Islet Amyloid Polypeptide Protein in a Membrane Environment by Solution NMR Spectroscopy
Nanga, R. P. R., Brender, J., Xu, J., Hartman, K. L., Vivekanandan, S., & Ramamoorthy, A. (2009) · Journal of the American Chemical Society · doi:10.1021/ja9010095 · Cited by 147
Structural Characterisation of Islet Amyloid Polypeptide Fibrils
Makin, O. S., & Serpell, L. C. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.11.048 · Cited by 147
Acceleration of amyloid protein A amyloidosis by amyloid-like synthetic fibrils
Johan, K., Westermark, G. T., Engström, U., Gustavsson, Å., Hultman, P. A., & Westermark, P. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2558 · Cited by 147
Self-citation
Analysis of amylin cleavage products provides new insights into the amyloidogenic region of human amylin
Nilsson, M. R., & Raleigh, D. P. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3286 · Cited by 146
Role of islet amyloid in type 2 diabetes mellitus
Höppener, J. W. M., & Lips, C. J. M. (2006) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.12.009 · Cited by 148
Design of Peptide-based Inhibitors of Human Islet Amyloid Polypeptide Fibrillogenesis
Scrocchi, L. A., Chen, Y., Waschuk, S., Wang, F., Cheung, S., Darabie, A. A., McLaurin, J., & Fraser, P. E. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00164-x · Cited by 143
Inhibition of IAPP and IAPP(20−29) Fibrillation by Polymeric Nanoparticles
Cabaleiro-Lago, C., Lynch, I., Dawson, K. A., & Linse, S. S. (2009) · Langmuir · doi:10.1021/la902980d · Cited by 142

Authors: Westermark, P., Engström, U., Johnson, K. H., Westermark, G. T., & Betsholtz, C.
Affiliations: Linköping University Hospital (SE)
ORCID: Westermark, P
Westermark, G T
Betsholtz, C
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1990-07
Volume: 87
Issue: 13
Pages: 5036-5040
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.87.13.5036
PMC: PMC54256
OpenAlex: W2061111679
Cited by: 807
References: 30
Citations by year: 2026: 18 · 2025: 20 · 2024: 27 · 2023: 17 · 2022: 25 · 2021: 31 · 2020: 43 · 2019: 21 · 2018: 28 · 2017: 41 · 2016: 36 · 2015: 36 · 2014: 29 · 2013: 33 · 2012: 36
FWCI: 7.26
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01dk036734-06)
Medical Research Council
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK36734)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
Keywords: amylin, amyloid fibril formation, type 2 diabetes, pancreatic beta cells, peptide aggregation
MeSH terms: Amino Acid Sequence, Amyloid, Amyloidosis, Animals, Cats, Diabetes Mellitus, Type 2, Cricetinae, Humans, Islets of Langerhans, Microscopy, Electron, Molecular Sequence Data, Mutation, Protein Precursors, Sequence Homology, Nucleic Acid, Species Specificity, Rats, Islet Amyloid Polypeptide

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation.

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks