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
Open accessAbstract
Aims/hypothesis Type II (non-insulin-dependent) diabetes mellitus is a multifactorial disease in which pancreatic islet amyloid is a characteristic histopathological finding. Islet amyloid fibrils consist of the beta-cell protein "islet amyloid polypeptide" (IAPP)/"amylin". Unlike human IAPP (hIAPP), mouse IAPP cannot form amyloid. In previously generated transgenic mice, high expression of hIAPP as such did not induce islet amyloid formation. To further explore the potential diabetogenic role of amyloidogenic IAPP, we introduced a diabetogenic trait ("ob" mutation) in hIAPP transgenic mice.Methods Plasma concentrations of IAPP, insulin and glucose were determined at 3.5 (t1), 6 (t2), and 16-19 months of age (t3). At t3, the mice were killed and the pancreas was analysed (immuno)histochemically.Results In non-transgenic ob/ob mice, insulin resistance caused a compensatory increase in insulin production, normalizing the initial hyperglycaemia. In transgenic ob/ob mice, concurrent increase in hIAPP production resulted in extensive islet amyloid formation (more often and more extensive than in transgenic non-ob/ob mice), insulin insufficiency and persistent hyperglycaemia: At t3, plasma insulin levels in transgenic ob/ob mice with amyloid were fourfold lower than in non-transgenic ob/ob mice (p < 0.05), and plasma glucose concentrations in transgenic ob/ ob mice were almost twofold higher (p < 0.05). In addition, the degree of islet amyloid formation in ob/ob mice was positively correlated to the glucose:insulin ratio (r(s) = 0.53, p < 0.05).Conclusion/interpretation Islet amyloid is a secondary diabetogenic factor which can be both a consequence of insulin resistance and a cause of insulin insufficiency. [Diabetol
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Studies using human IAPP transgenic mice suggest that increased dietary fat or marked overproduction of IAPP could trigger the commencement of islet amyloidogenesis.
“Studies using human IAPP transgenic mice suggest that consumption of increased dietary fat [133] or marked overproduction of IAPP [134, 135] could be important factors in triggering the commencement of islet amyloidogenesis.”
From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [135]
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Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419 · see citing works
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus* (2002) · Diabetes Care · doi:10.2337/diacare.25.2007.s5 · Cited by 10,320 · see citing works
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1995) · Nature · doi:10.1038/374479a0 · Cited by 1,125 · see citing works
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 · see citing works
Slot, J. W., Geuze, H. J., Gigengack, S., Lienhard, G. E., & James, D. E. (1991) · The Journal of Cell Biology · doi:10.1083/jcb.113.1.123 · Cited by 862 · see citing works
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 819 · see citing works
Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation.
Westermark, P., Engström, U., Johnson, K. H., Westermark, G. T., & Betsholtz, C. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.13.5036 · Cited by 807 · see citing works
Clark, A., Wells, C. A., BULEY, I. D., Cruickshank, J. K., Vanhegan, R. I., Matthews, D. R., Cooper, G. J. S., Holman, R. R., & Turner, R. C. (1988) · PubMed · Cited by 518 · see citing works
Improving structural integrity of cryosections for immunogold labeling
Liou, W., Geuze, H. J., & Slot, J. W. (1996) · Histochemistry and Cell Biology · doi:10.1007/bf02473201 · Cited by 507 · see citing works
Evidence of Cosecretion of Islet Amyloid Polypeptide and Insulin by β-Cells
Kahn, S. E., D'Alessio, D. A., Schwartz, M. W., Fujimoto, W. Y., Ensinck, J. W., Taborsky, G. J., & Porte, D. (1990) · Diabetes · doi:10.2337/diab.39.5.634 · Cited by 454 · see citing works
Type 2 Diabetes: When Insulin Secretion Fails to Compensate for Insulin Resistance
Kahn, B. B. (1998) · Cell · doi:10.1016/s0092-8674(00)81125-3 · Cited by 426 · see citing works
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 348 · see citing works
Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide.
Janson, J., Soeller, W. C., Roche, P. C., Nelson, R. T., Torchia, A. J., Kreutter, D. K., & Butler, P. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.14.7283 · Cited by 343 · see citing works
GENETICS OF NON-INSULIN-DEPENDENT (TYPE-II) DIABETES MELLITUS
Kahn, C. R., Vicent, D., & Doria, A. (1996) · Annual Review of Medicine · doi:10.1146/annurev.med.47.1.509 · Cited by 211 · see citing works
German, M. S., Moss, L. G., Wang, J., et al. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.4.1777 · Cited by 167 · see citing works
Longitudinal studies on the development of diabetes in individual Macaca nigra
Howard, C. F. (1986) · Diabetologia · doi:10.1007/bf00452067 · Cited by 141 · see citing works
Islet amyloid-associated diabetes in obese A(vy)/a mice expressing human islet amyloid polypeptide.
Soeller, W. C., Janson, J., Hart, S. E., Parker, J. C., Carty, M. D., Stevenson, R. W., Kreutter, D. K., & Butler, P. C. (1998) · Diabetes · doi:10.2337/diabetes.47.5.743 · Cited by 140 · see citing works
Serup, P., Jensen, J. N., Andersen, F. G., Jørgensen, M. C., Blume, N., Holst, J. J., & Madsen, O. D. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.17.9015 · Cited by 136 · see citing works
Amyloid in polypeptide hormone-producing tumors.
Westermark, P., Grimelius, L., Polak, J. M., et al. (1977) · PubMed · Cited by 114 · see citing works
Röcken, C., LINKE, R. P., & Saeger, W. (1992) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/bf01660981 · Cited by 81 · see citing works
Evidence of cosecretion of islet amyloid polypeptide and insulin by beta-cells
Kahn, S. E., D’Alessio, D. A., Schwartz, M. W., Fujimoto, W. Y., Ensinck, J. W., Taborsky, G., & Porte, D. (1990) · Diabetes · doi:10.2337/diabetes.39.5.634 · Cited by 69 · see citing works
Larsson, H. E., & Ahr�n, B. (1996) · Diabetologia · doi:10.1007/bf00400660 · Cited by 60 · see citing works
Self-citationLarsson, H., & Ahr�n, B. (1996) · Diabetologia · doi:10.1007/s001250050559 · Cited by 60 · see citing works
Self-citationMulder, H., Åhrén, B., & Sundler, F. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.271.6.e1008 · Cited by 48 · see citing works
German, M. S., Moss, L. G., Wang, J., et al. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.4.1777-1788.1992 · Cited by 47 · see citing works
Åhrén, B., Oosterwijk, C., Lips, C. J. M., & Höppener, J. W. M. (1998) · Diabetologia · doi:10.1007/s001250051079 · Cited by 43 · see citing works
Self-citationImproving structural integrity of cryosections for immunogold labeling
Liou, W., Geuze, H. J., & Slot, J. W. (1996) · Histochemistry and Cell Biology · doi:10.1007/s004180050022 · Cited by 43 · see citing works
The Diabetogenes Concept of NIDDM
MEYTS, P. D. (1993) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-2910-1_7 · Cited by 24 · see citing works
An Improved Method for the Determination of Islet Amyloid Polypeptide Levels in Plasma
van Hulst, K. L., Hackeng, W. H. L., Höppener, J. W. M., van Jaarsveld, B. C., Nieuwenhuis, M. G., Blankenstein, M. A., & Lips, C. J. M. (1994) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/000456329403100209 · Cited by 20 · see citing works
Self-citationCounterregulatory hormone and symptom responses to hypoglycaemia in diabetic children
Bjørgaas, M. R., Vik, T., Sand, T., Birkeland, K. I., Sager, G., Vea, H., & Jorde, R. (1997) · Diabetic Medicine · doi:10.1002/(sici)1096-9136(199706)14:6 · Cited by 15 · see citing works
Diabetes in midlife: Planting genetic time bombs
O’Rahilly, S. (1997) · Nature Medicine · doi:10.1038/nm1097-1080 · Cited by 8 · see citing works
Pancreatic islet amyloid formation in patients with noninsulin-dependent diabetes mellitus
Oosterwijk, C., Höppener, J. W. M., van Hulst, K. L., & Lips, C. J. M. (1995) · International Journal of Gastrointestinal Cancer · doi:10.1007/bf02825416 · Cited by 7 · see citing works
Self-citationTransient postweaning expression of excessive fat deposition and diabetes mellitus in ob/ob mice.
Dubuc, P. U. (1997) · PubMed · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kahn, S. E. (2003) · Diabetologia · doi:10.1007/s00125-002-1009-0 · Cited by 2,166 · see citing works
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 · see citing works
Butler, A. E., Janson, J., Soeller, W. C., & Butler, P. C. (2003) · Diabetes · doi:10.2337/diabetes.52.9.2304 · Cited by 411 · see citing works
Qiao, Q., Bowman, G. R., & Huang, X. (2013) · Journal of the American Chemical Society · doi:10.1021/ja403147m · Cited by 182 · see citing works
Endoplasmic Reticulum Stress and Diabetes Mellitus.
ARAKI, E., OYADOMARI, S., & MORI, M. (2003) · Internal Medicine · doi:10.2169/internalmedicine.42.7 · Cited by 151 · see citing works
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 · see citing works
Wang, F., Hull, R. L., Vidal, J., Cnop, M., & Kahn, S. E. (2001) · Diabetes · doi:10.2337/diabetes.50.11.2514 · Cited by 77 · see citing works
Muff, R., Born, W., Lutz, T. A., & Fischer, J. A. (2004) · Peptides · doi:10.1016/j.peptides.2004.08.007 · Cited by 62 · see citing works
- Authors
- Höppener, J. W. M., Oosterwijk, C., Nieuwenhuis, M. G., Posthuma, G., Thijssen, J. H. H., Vroom, T. M., Ahrén, B., & Lips, C. J. M.
- Affiliations
- Utrecht University (NL)
- Venue
- Diabetologia
- Published
- 1999-03-19
- Volume
- 42
- Issue
- 4
- Pages
- 427-434
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2085244013
- Cited by
- 153
- References
- 33
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 6 · 2012: 3
- FWCI
- 8.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universiteit Utrecht
- Lunds Universitet
- Malmö Högskola
- Universitätsklinikum Tübingen
- Medical Research Council
- Medicinska Fakulteten, Lunds Universitet
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- islet amyloid, type 2 diabetes, amylin, insulin resistance, insulin deficiency, hyperglycemia, pancreatic beta cells, transgenic mice, diabetes pathogenesis, glucose/insulin ratio
- MeSH terms
- Amyloid, Animals, Blood Glucose, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Female, Humans, Insulin, Islets of Langerhans, Male, Mice, Inbred C57BL, Mice, Obese, Mice, Transgenic, Point Mutation, Mice, Islet Amyloid Polypeptide
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