Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation
Open accessAbstract
Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 cells as a β-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway.
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Increased oxidative stress and JNK/MAPK expression can contribute to pancreatic β-cell dysfunction with apoptosis, glucose-induced insulin secretion impairment, and subsequent insulin resistance, a key hallmark of type 2 DM.
“Furthermore, increased oxidative stress and JNK/MAPK expression can contribute to pancreatic β-cell dysfunction with apoptosis, glucose-induced insulin secretion impairment, and subsequent insulin resistance, which is a key hallmark of type 2 DM54.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [54]
Another mechanism underlying AGEs' ability to inhibit insulin secretion is activation of P38/MAPK and downstream disturbance of microtubule dynamics, marked by increased microtubule depolymerization in pancreatic β-cells in culture.
“Another mechanism which, albeit in part, underlies the ability of AGEs to inhibit insulin secretion is the activation of P38/mitogen-activated protein kinase (MAPK) and the downstream disturbance of microtubule dynamics marked by an increase in microtubule depolymerization in pancreatic 𝛽-cells in culture.[139]”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [139]
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Cites
Calcium's Role in Mechanotransduction during Muscle Development
Damm, T. B., & Egli, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356667 · Cited by 14,548 · see citing works
Advanced glycation end-products: A review
Singh, R., Barden, A., Mori, T., & Beilin, L. (2001) · Diabetologia · doi:10.1007/s001250051591 · Cited by 2,597 · see citing works
Roux, P. P., & Blenis, J. (2004) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.68.2.320-344.2004 · Cited by 2,494 · see citing works
Activation and signaling of the p38 MAP kinase pathway
Zarubin, T., & Han, J. (2005) · Cell Research · doi:10.1038/sj.cr.7290257 · Cited by 1,711 · see citing works
Establishment of 2-mercaptoethanol-dependent differentiated insulin- secreting cell lines
Asfari, M., Janjic, D., Meda, P., Li, G., Halban, P. A., & Wollheim, C. B. (1992) · Endocrinology · doi:10.1210/endo.130.1.1370150 · Cited by 1,165 · see citing works
Advanced Glycation End Products and Oxidative Stress in Type 2 Diabetes Mellitus
Nowotny, K., Jung, T., Höhn, A., Weber, D., & Grune, T. (2015) · Biomolecules · doi:10.3390/biom5010194 · Cited by 1,095 · see citing works
Giannakakou, P., Sackett, D. L., Kang, Y., Zhan, Z., Buters, J., Fojo, T., & Poruchynsky, M. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.27.17118 · Cited by 682 · see citing works
The importance of the β-cell in the pathogenesis of type 2 diabetes mellitus
Kahn, S. E. (2000) · The American Journal of Medicine · doi:10.1016/s0002-9343(00)00336-3 · Cited by 242 · see citing works
Minotti, A., Barlow, S. B., & Cabral, F. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)67891-9 · Cited by 222 · see citing works
Hironori Nakagami, A., Morishita, R., Yamamoto, K., Yoshimura, S.-I., Taniyama, Y., Aoki, M., Matsubara, H., Kim, S., Kaneda, Y., & Ogihara, T. (2001) · Diabetes · doi:10.2337/diabetes.50.6.1472 · Cited by 163 · see citing works
Zhao, Z., Zhao, C., Zhang, X. H., Zheng, F., Cai, W., Vlassara, H., & Ma, Z. A. (2009) · Endocrinology · doi:10.1210/en.2008-1342 · Cited by 132 · see citing works
ROLE OF MICROTUBULES IN THE PHASIC PATTERN OF INSULIN RELEASE*
Malaisse, W. J., MALAISSE-LAGAE, F., OBBERGHEN, E. V., Somers, G., Devis, G., Ravazzola, M., & Orci, L. (1975) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1975.tb19234.x · Cited by 131 · see citing works
Advanced glycation end-products induce injury to pancreatic beta cells through oxidative stress
Lin, N., Zhang, H., & Su, Q. (2012) · Diabetes & Metabolism · doi:10.1016/j.diabet.2012.01.003 · Cited by 103 · see citing works
Dynamics of insulin release and microtubular-microfilamentous system
Devis, G., OBBERGHEN, E. V., Somers, G., MALAISSE-LAGAE, F., Orci, L., & Malaisse, W. J. (1974) · Diabetologia · doi:10.1007/bf00421414 · Cited by 83 · see citing works
Li, L., Hu, J., He, T., Zhang, Q., Yang, X., Lan, X., Zhang, D., Mei, H., Chen, B., & Huang, Y. (2015) · Scientific Reports · doi:10.1038/srep08895 · Cited by 82 · see citing works
Lim, M., Park, L., Shin, G., Hong, H., Kang, I., & Park, Y. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1447.011 · Cited by 81 · see citing works
Hu, J., Chu, Z., Han, J., Dang, Y.-M., Yan, H., Zhang, Q., Liang, G., & Huang, Y. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0187-z · Cited by 80 · see citing works
Inhibition of the receptor for advanced glycation endproducts (RAGE) protects pancreatic β-cells
Zhu, Y., Shu, T., Yan, L., Wang, H., Yang, J., Shi, Y., & Han, X. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.11.085 · Cited by 79 · see citing works
Heaslip, A. T., Nelson, S. R., Lombardo, A. T., Previs, S. B., Armstrong, J. M., & Warshaw, D. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109082 · Cited by 74 · see citing works
Motile Events in Pancreatic Endocrine Cells*
Somers, G., Blondel, B., Orci, L., & Malaisse, W. J. (1979) · Endocrinology · doi:10.1210/endo-104-1-255 · Cited by 70 · see citing works
Cui, J., Wang, Z., Cheng, Q., Lin, R., Zhang, X.-M., Leung, P. S., Copeland, N. G., Jenkins, N. A., Yao, K., & Huang, J. (2010) · Diabetes · doi:10.2337/db09-1078 · Cited by 62 · see citing works
Self-citationSrinivasan, S. R., Bolick, D. T., Hatley, M. E., Natarajan, R. D., Reilly, K. B., Yeh, M. W., Chrestensen, C. A., Sturgill, T. W., & Hedrick, C. C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400753200 · Cited by 58 · see citing works
Shu, T., Zhu, Y., Wang, H., Lin, Y., Ma, Z., & Han, X. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018782 · Cited by 51 · see citing works
Microtubules, microfilaments and insulin secretion
Howell, S. L., & Tyhurst, M. (1982) · Diabetologia · doi:10.1007/bf00253571 · Cited by 43 · see citing works
Advanced Glycation End-Products affect transcription factors regulating insulin gene expression
Puddu, A., Storace, D., Odetti, P. R., & Viviani, G. L. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.03.152 · Cited by 40 · see citing works
Cinemicrographic studies on beta granule movement in monolayer culture of islet cells.
Pe, L., Finke, E. H., & Rc, C. (1975) · PubMed · Cited by 40 · see citing works
Dynamics of Insulin Release and Microtubular‐Microfilamentous System
Somers, G., OBBERGHEN, E. V., Devis, G., Ravazzola, M., MALAISSE-LAGAE, F., & Malaisse, W. J. (1974) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1974.tb02349.x · Cited by 39 · see citing works
Bansal, S., Chawla, D., Banerjee, B. D., Madhu, S. V., & Tripathi, A. K. (2013) · Gene · doi:10.1016/j.gene.2013.05.013 · Cited by 24 · see citing works
Farshori, P., & Goode, D. (1994) · PubMed · Cited by 22 · see citing works
Glycated Albumin Causes Pancreatic β-Cells Dysfunction Through Autophagy Dysfunction
Song, Y., Song, S. O., You, Y., Yoon, K., Kang, E. S., Soo, B., Lee, H. C., Kim, J., & Lee, B. (2013) · Endocrinology · doi:10.1210/en.2013-1031 · Cited by 20 · see citing works
Bollheimer, L. C., Wrede, C. E., Rockmann, F., Ottinger, I., Schölmerich, J., & Buettner, R. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.01.168 · Cited by 19 · see citing works
Colocalization of insulin and glucagon in insulinoma cells and developing pancreatic endocrine cells
Wang, Z., You, J., Xu, S., Hua, Z., Zhang, W., Deng, T., Ni, F., Fang, Q., Liu, H., Peng, L., et al. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.04.072 · Cited by 10 · see citing works
Self-citationKanazawa, Y., Kawazu, S., Ikeuchi, M., & Kosáka, K. (1980) · Diabetes · doi:10.2337/diab.29.12.953 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Rungratanawanich, W., Qu, Y., Wang, X., Essa, M. M., & Song, B.-J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00561-7 · Cited by 411 · see citing works
The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction
Sergi, D., Boulestin, H., Campbell, F. M., & Williams, L. M. (2021) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900934 · Cited by 194 · see citing works
Gutierrez‐Mariscal, F. M., Cardelo, M. P., de la Cruz, S., Alcala‐Diaz, J. F., Roncero‐Ramos, I., Guler, I., Vals‐Delgado, C., López‐Moreno, A., Luque, R. M., Delgado‐Lista, J., et al. (2021) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201901290 · Cited by 60 · see citing works
Zhang, J., Li, L., Zhang, Q., Wang, W., Zhang, D., Jia, J., Lv, Y., Yuan, H., Song, H., Xiang, F., et al. (2019) · International Journal of Biological Sciences · doi:10.7150/ijbs.35440 · Cited by 38 · see citing works
An update on the potential role of advanced glycation end products in glycolipid metabolism
Wang, X., Liu, J., Ying, Y., & Zhang, X. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117344 · Cited by 32 · see citing works
Hou, Y., Ding, W., Wu, P., Liu, C., Ding, L., Liu, J., & Wang, X. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02760-z · Cited by 29 · see citing works
Zhang, J., Li, L., Zhang, Q., Yang, X., Zhang, C. M., Zhang, X., Zhang, D., Lv, Y., Song, H., Chen, B., et al. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00368 · Cited by 25 · see citing works
Miyazaki, S., Tashiro, F., Tsuchiya, T., Sasaki, K., & Miyazaki, J. (2021) · Scientific Reports · doi:10.1038/s41598-020-79992-7 · Cited by 23 · see citing works
Xu, J., Fu, C., Li, T., Xia, X., Zhang, H., Wang, X., & Zhao, Y. (2020) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2020.113444 · Cited by 22 · see citing works
Sha, J., Song, J., Huang, Y., Zhang, Y., Wang, H., Zhang, Y., & Suo, H. (2021) · Foods · doi:10.3390/foods11010080 · Cited by 15 · see citing works
Linderane protects pancreatic β cells from streptozotocin (STZ)-induced oxidative damage
Zhang, H., Zhu, C., Sun, Z., XiaoGuang, Y., Wang, H. H., Xu, H., Ma, J., & Zhang, Y. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.116732 · Cited by 15 · see citing works
Dysfunction of SERCA pumps as novel mechanism of methylglyoxal cytotoxicity
Žižková, P., Viskupičová, J., Heger, V., Račková, L., Májeková, M., & Horáková, Ľ. (2018) · Cell Calcium · doi:10.1016/j.ceca.2018.06.003 · Cited by 11 · see citing works
Anastasiou, I. A., Tentolouris, K. N., Lambadiari, V., Eleftheriadou, I., Tektonidou, M. G., & Tentolouris, N. (2023) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557523666230510123038 · Cited by 7 · see citing works
Borg, D. J., Faridi, P., Giam, K., Reeves, P., Fotheringham, A. K., McCarthy, D. A., Leung, S. S., Ward, M. S., Harcourt, B. E., Ayala, R., et al. (2021) · Metabolites · doi:10.3390/metabo11070426 · Cited by 2 · see citing works
Anand, S., Kantari, K., Kumar, P., Pradhan, S. S., & Agraharam, A. (2025) · Network Modeling Analysis in Health Informatics and Bioinformatics · doi:10.1007/s13721-025-00618-x · Cited by 1 · see citing works
Duan, S., Zhou, Q., Shi, Y., Ye, Y., Hua, H., Liu, D., Xue, Y., Zhang, C., Yuan, Y., Xing, C., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27114696 · Cited by 1 · see citing works
Hasannuri, T. R., Syamsunarno, M. R. A. A., & Putra, A. (2024) · HAYATI Journal of Biosciences · doi:10.4308/hjb.31.5.988-995
Li, D., Huang, Y. N., Chen, X.-Q., Lp, Z., Gong, Q., Li, Q., Li, Y., Xu, Y., & Huang, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1886016
- Authors
- You, J., Wang, Z., Xu, S., Zhang, W., Fang, Q., Liu, H., Peng, L., Deng, T., & Lou, J.
- Affiliations
- China-Japan Friendship Hospital (CN)
- Corresponding author
- Lou, Jinning
- Venue
- Journal of Diabetes Research
- Publisher
- Wiley
- Published
- 2016
- Volume
- 2016
- Pages
- 1-9
- ISSN
- 2314-6745 (ISSN-L)
- 2314-6753
- PMC
- PMC5011238
- OpenAlex
- W2516977151
- Cited by
- 18
- References
- 33
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 1
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Diabetes Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81302334, 81370873, 81200616, 2015-QNYC-B-06, 2014-QNYC-A-05, 2012CB966402)
- China-Japan Friendship Hospital Youth Science and Technology Excellence Project (81302334, 81370873, 81200616, 2015-QNYC-B-06, 2014-QNYC-A-05, 2012CB966402)
- National Basic Research Program of China (81302334, 81370873, 81200616, 2015-QNYC-B-06, 2014-QNYC-A-05, 2012CB966402)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Keywords
- advanced glycation end products, insulin secretion, pancreatic beta cells, microtubule dynamics, microtubule depolymerization, p38 MAPK signaling, SB202190, beta-cell dysfunction, diabetes mellitus, cytotoxicity
- MeSH terms
- Insulin Secretion, Animals, Cell Line, Cytoskeleton, Glucose, Insulin, Microtubules, Signal Transduction, Glycation End Products, Advanced, p38 Mitogen-Activated Protein Kinases, Insulin-Secreting Cells, Rats
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