The DOI matches its Crossref record; 64 of the 66 references it cites were found in a registry or an index.
Epigenetic mechanisms in the development of type 2 diabetes
Open accessAbstract
Type 2 diabetes (T2D) is a disorder of complex genetics influenced by interactions between susceptible genetic loci and environmental perturbations. Intrauterine growth retardation is one such environmental perturbation linked to the development of T2D in adulthood. An abnormal metabolic intrauterine milieu affects fetal development by permanently modifying expression of key genes regulating beta-cell development (Pdx1) and glucose transport (Glut4) in muscle. Epigenetic regulation of gene expression is one mechanism by which genetic susceptibility and environmental insults can lead to T2D. Therefore, therapeutic agents targeting epigenetic gene regulation can ultimately be used to treat T2D; however, there is much to be learned about genome-wide epigenetic programming of health and disease before these therapies can be used in patient care.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This loss of β-cell mass has been linked to epigenetic downregulation of pancreatic homeobox transcription factor (Pdx1), which is essential for normal β-cell differentiation in the embryo [79].”
From The Pathophysiology of Gestational Diabetes Mellitus (2018) · cites this paper as [79]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Aberrant promoter methylation of multiple genes during multistep pathogenesis of colorectal cancers
Takahashi, T., Shigematsu, H., Shivapurkar, N., Reddy, J., Zheng, Y., Feng, Z., Suzuki, M., Nomura, M., Augustus, M., Yin, J., et al. (2005) · International Journal of Cancer · doi:10.1002/ijc.21453 · Cited by 42
RetractedWild, S., Roglic, G., Green, A., Sicree, R., & King, H. (2004) · Diabetes Care · doi:10.2337/diacare.27.5.1047 · Cited by 15,297
Glass, C. K., & Witztum, J. L. (2001) · Cell · doi:10.1016/s0092-8674(01)00238-0 · Cited by 3,094
Fetal and infant growth and impaired glucose tolerance at age 64
Hales, C. N., Barker, D. J., Clark, P. M., Cox, L. J., Fall, C., Osmond, C., & Winter, P. D. (1991) · BMJ · doi:10.1136/bmj.303.6809.1019 · Cited by 2,708
Linking DNA methylation and histone modification: patterns and paradigms
Cedar, H., & Bergman, Y. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2540 · Cited by 2,267
Obesity at the age of 50 y in men and women exposed to famine prenatally
Ravelli, A. C. J., van der Meulen, J., Osmond, C., Barker, D. J. P., & Bleker, O. P. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/70.5.811 · Cited by 1,165
Monk, M., Boubelı́k, M., & Lehnert, S. A. (1987) · Development · doi:10.1242/dev.99.3.371 · Cited by 1,100
Genomic and Epigenetic Instability in Colorectal Cancer Pathogenesis
Grady, W. M., & Carethers, J. M. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.07.076 · Cited by 991
A high-resolution map of active promoters in the human genome
Kim, T. H., Barrera, L. O., Zheng, M., Qu, C., Singer, M. A., Richmond, T., Wu, Y., Green, R. D., & Ren, B. (2005) · Nature · doi:10.1038/nature03877 · Cited by 954
Histone methylation in transcriptional control
Kouzarides, T. (2002) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00287-3 · Cited by 908
Maternal Methyl Supplements in Mice Affect Epigenetic Variation and DNA Methylation of Offspring
Cooney, C. A., Dave, A. A., & Wolff, G. L. (2002) · Journal of Nutrition · doi:10.1093/jn/132.8.2393s · Cited by 784
Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line.Preprint
Kafri, T., Ariel, M. S., Brandeis, M., Shemer, R., Urven, L. E., McCarrey, J. R., Cedar, H., & Razin, A. (1992) · Genes & Development · doi:10.1101/gad.6.5.705 · Cited by 743
Sakuraba, H., Mizukami, H., Yagihashi, N., Wada, R., Hanyu, C., & Yagihashi, S. (2002) · Diabetologia · doi:10.1007/s125-002-8248-z · Cited by 699
Park, J. H., Stoffers, D. A., Nicholls, R. D., & Simmons, R. A. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33655 · Cited by 640
Self-citationIntrauterine Growth Retardation Leads to the Development of Type 2 Diabetes in the Rat
Simmons, R. A., Templeton, L. J., & Gertz, S. J. (2001) · Diabetes · doi:10.2337/diabetes.50.10.2279 · Cited by 638
Self-citationRNA meets chromatinPreprint
Bernstein, E., & Allis, C. D. (2005) · Genes & Development · doi:10.1101/gad.1324305 · Cited by 629
Decline in genomic DNA methylation through aging in a cohort of elderly subjects
Bollati, V., Schwartz, J. D., Wright, R. O., Litonjua, A. A., Tarantini, L., Suh, H. H., Sparrow, D., Vokonas, P., & Baccarelli, A. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.12.003 · Cited by 618
Oxidative stress, DNA methylation and carcinogenesis
Franco, R., Schoneveld, O., Georgakilas, A. G., & Panayiotidis, M. I. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.02.026 · Cited by 603
Brasacchio, D., Okabe, J., Tikellis, C., Balcerczyk, A., George, P., Baker, E. K., Calkin, A. C., Brownlee, M., Cooper, M. E., & El‐Osta, A. (2009) · Diabetes · doi:10.2337/db08-1666 · Cited by 538
Ihara, Y., Toyokuni, S., Uchida, K., Odaka, H., Tanaka, T., Ikeda, H., Hiai, H., Seino, Y., & Yamada, Y. (1999) · Diabetes · doi:10.2337/diabetes.48.4.927 · Cited by 506
Bannister, A. J., & Kouzarides, T. (2005) · Nature · doi:10.1038/nature04048 · Cited by 503
Silva, J. P., Köhler, M., Graff, C., Oldfors, A., Magnuson, M. A., Berggren, P.-O., & Larsson, N.-G. (2000) · Nature Genetics · doi:10.1038/81649 · Cited by 433
Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene
Bachman, K. E., Park, B. H., Rhee, I. P., Rajagopalan, H., Herman, J. G., Baylin, S. B., Kinzler, K. W., & Vogelstein, B. (2003) · Cancer Cell · doi:10.1016/s1535-6108(02)00234-9 · Cited by 419
β-Cell Mass Dynamics in Zucker Diabetic Fatty Rats
Finegood, D. T., McArthur, M. D., Kojwang, D., Thomas, M. J., Topp, B. G., Leonard, T. B., & Buckingham, R. E. (2001) · Diabetes · doi:10.2337/diabetes.50.5.1021 · Cited by 375
On the origin of the β cellPreprint
Oliver-Krasinski, J. M., & Stoffers, D. A. (2008) · Genes & Development · doi:10.1101/gad.1670808 · Cited by 361
Li, H., Rauch, T. A., Chen, Z.-X., Szabó, P. E., Riggs, A. D., & Pfeifer, G. P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513249200 · Cited by 352
Kaneto, H., Xu, G., Song, K., Suzuma, K., Bonner‐Weir, S., Sharma, A., & Weir, G. C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104115200 · Cited by 327
Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic β-cells
Sakai, K., Matsumoto, K., Nishikawa, T., Suefuji, M., Nakamaru, K., Hirashima, Y., Kawashima, J., Shirotani, T., Ichinose, K., Brownlee, M., et al. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02832-2 · Cited by 323
The role of chromatin structure in regulating the expression of clustered genes
Sproul, D., Gilbert, N., & Bickmore, W. A. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1688 · Cited by 310
Low birthweight is associated with specific changes in muscle insulin-signalling protein expression
Ozanne, S. E., Jensen, C. B., Tingey, K., Storgaard, H., Madsbad, S., & Vaag, A. A. (2005) · Diabetologia · doi:10.1007/s00125-005-1669-7 · Cited by 290
Rauch, T. A., Wang, Z., Zhang, X., Zhong, X., Wu, X., Lau, S. K., Kernstine, K. H., Riggs, A. D., & Pfeifer, G. P. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701059104 · Cited by 285
Predicting aberrant CpG island methylation
Feltus, F. A., Lee, E. K., Costello, J., Plass, C., & Vertino, P. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2037852100 · Cited by 281
DNA methylation in development and human disease
Gopalakrishnan, S., Emburgh, B. O. V., & Robertson, K. D. (2008) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2008.08.006 · Cited by 271
Neonatal Exendin-4 Prevents the Development of Diabetes in the Intrauterine Growth Retarded Rat
Stoffers, D. A., Desai, B. M., León, D. D. D., & Simmons, R. A. (2003) · Diabetes · doi:10.2337/diabetes.52.3.734 · Cited by 263
Self-citationAn epigenetic perspective on the free radical theory of development
Hitchler, M. J., & Domann, F. E. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.06.027 · Cited by 241
Higa, M., Zhou, Y.-T., Ravazzola, M., Baetens, D., Orci, L., & Unger, R. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11513 · Cited by 233
Raychaudhuri, N., Raychaudhuri, S., Thamotharan, M., & Devaskar, S. U. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800128200 · Cited by 232
MacLennan, N. K., James, S., Melnyk, S., Piroozi, A., Jernigan, S., Hsu, J., Janke, S., Pham, T. D., & Lane, R. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00042.2004 · Cited by 224
The Dynamics of Chromatin Remodeling at Promoters
Mellor, J. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.06.023 · Cited by 221
Simmons, R. A., Suponitsky-Kroyter, I., & Selak, M. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505695200 · Cited by 194
Self-citationBernardo, A. S., Hay, C. W., & Docherty, K. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.07.006 · Cited by 169
Schübeler, D., Lorincz, M. C., Cimbora, D. M., Telling, A., Feng, Y.-Q., Bouhassira, E. E., & Groudine, M. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.24.9103-9112.2000 · Cited by 165
The nuclear factor‐κB/inhibitor of kappa B autoregulatory system and atherosclerosis
Thurberg, B. L., & Collins, T. (1998) · Current Opinion in Lipidology · doi:10.1097/00041433-199810000-00002 · Cited by 154
Evans‐Molina, C., Robbins, R. D., Kono, T., Tersey, S. A., Vestermark, G. L., Nunemaker, C. S., Garmey, J. C., Deering, T. G., Keller, S. R., Maier, B., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01179-08 · Cited by 147
Karnieli, E., & Armoni, M. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90306.2008 · Cited by 144
Tikoo, K., Meena, R., Kabra, D. G., & Gaikwad, A. B. (2008) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707666 · Cited by 144
Yoshida, H., Broaddus, R. R., Cheng, W., Xie, S.-S., & Naora, H. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2828 · Cited by 141
So, K., Tamura, G., Honda, T., Homma, N., Waki, T., Togawa, N., Nishizuka, S., & Motoyama, T. (2006) · Cancer Science · doi:10.1111/j.1349-7006.2006.00302.x · Cited by 122
Fu, Q., McKnight, R., Yu, X., Wang, L., Callaway, C., & Lane, R. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00175.2004 · Cited by 120
The Genetics of Type 2 Diabetes: A Realistic Appraisal in 2008
Florez, J. C. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1345 · Cited by 118
Neu, J. (2009) · Yearbook of Neonatal and Perinatal Medicine · doi:10.1016/s8756-5005(08)79286-2 · Cited by 92
Pancreatic Islet Expression of the Homeobox Factor STF-1 Relies on an E-box Motif That Binds USF
Sharma, S., Leonard, J. N., Lee, S., Chapman, H. D., Leiter, E. H., & Montminy, M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.4.2294 · Cited by 87
Thamotharan, M., Shin, B., Suddirikku, D. T., Thamotharan, S., Garg, M., & Devaskar, S. (2005) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.00342.2004 · Cited by 82
Genetic determinants and molecular pathways in the pathogenesis of Type 2 diabetes
Jin, W., & Patti, M. (2008) · Clinical Science · doi:10.1042/cs20080090 · Cited by 78
4-Hydroxynonenal oxidatively modifies histones: implications for Alzheimer's disease
Drake, J., Petroze, R. T., Castegna, A., Ding, Q., Keller, J. N., Markesbery, W. R., Lovell, M. A., & Butterfield, D. A. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2003.11.047 · Cited by 77
Fueger, P. T., Shearer, J., Bracy, D. P., Posey, K. A., Pencek, R., McGuinness, O. P., & Wasserman, D. H. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.076158 · Cited by 68
Applying whole-genome studies of epigenetic regulation to study human disease
Lieb, J. D., Beck, S., Bulyk, M. L., Farnham, P., Hattori, N., Henikoff, S., Liu, X. S., Okumura, K., Shiota, K., Ushijima, T., et al. (2006) · Cytogenetic and Genome Research · doi:10.1159/000091922 · Cited by 65
Upstream stimulatory factor regulates Pdx-1 gene expression in differentiated pancreatic β-cells
Qian, J., Kaytor, E. N., Towle, H. C., & Olson, L. K. (1999) · Biochemical Journal · doi:10.1042/0264-6021:3410315 · Cited by 61
Upstream stimulatory factor regulates Pdx-1 gene expression in differentiated pancreatic beta-cells.
Qian, J., Kaytor, E. N., Towle, H. C., & Olson, L. K. (1999) · PubMed Central · Cited by 58
Moreno, H., Serrano, A. L., Santalucı́a, T., Gumà, A., Cantó, C., Brand, N. J., Palacı́n, M., Schiaffino, S., & Zorzano, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306609200 · Cited by 54
Ruchko, M. V., Gorodnya, O. M., Pastukh, V. M., Swiger, B. M., Middleton, N. S., Wilson, G. L., & Gillespie, M. N. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.09.038 · Cited by 45
Kim, S., Nian, C., & McIntosh, C. H. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m809046200 · Cited by 35
Environmental influence on epigenetic inheritance at the Avy allele
Martin, D. I. K., Cropley, J. E., & Suter, C. M. (2008) · Nutrition Reviews · doi:10.1111/j.1753-4887.2008.00057.x · Cited by 21
Cited by
Sorted by citations
The worldwide epidemiology of type 2 diabetes mellitus—present and future perspectives
Chen, L., Magliano, D. J., & Zimmet, P. Z. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.183 · Cited by 2,227
The Pathophysiology of Gestational Diabetes Mellitus
Plows, J. F., Stanley, J. L., Baker, P. N., Reynolds, C. M., & Vickers, M. H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113342 · Cited by 1,874
“This loss of β-cell mass has been linked to epigenetic downregulation of pancreatic homeobox transcription factor (Pdx1), which is essential for normal β-cell differentiation in the embryo [79].”
BackgroundEarly Life Programming and Neurodevelopmental Disorders
Bale, T. L., Baram, T. Z., Brown, A. S., Goldstein, J. M., Insel, T. R., McCarthy, M. M., Nemeroff, C. B., Reyes, T. M., Simerly, R. B., Susser, E. S., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.05.028 · Cited by 961
Type 2 diabetes across generations: from pathophysiology to prevention and management
Nolan, C. J., Damm, P., & Prentki, M. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60614-4 · Cited by 923
(2014) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2013.10.012 · Cited by 914
Metadata
- Authors
- Pinney, S. E., & Simmons, R. A.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 21
- Issue
- 4
- Pages
- 223-229
- ISSN
- 1043-2760 (ISSN-L)
- PMC
- PMC2848901
- OpenAlex
- W1977200537
- Cited by
- 205
- References
- 66
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 9 · 2020: 8 · 2019: 7 · 2018: 11 · 2017: 13 · 2016: 14 · 2015: 17 · 2014: 22 · 2013: 27 · 2012: 19
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG020898)
- National Institute of Diabetes and Digestive and Kidney Diseases (L40 DK079770, R01DK055704, DK-55704)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD0432545)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- type 2 diabetes, epigenetic regulation, fetal growth restriction, fetal programming, beta-cell development, PDX1, GLUT4, gene-environment interaction, epigenetic therapy, gene expression
- MeSH terms
- Diabetes Mellitus, Type 2, Fetal Growth Retardation, Gene Expression Regulation, Histones, Humans, Trans-Activators, Oxidative Stress, Homeodomain Proteins, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Glucose Transporter Type 4
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
