Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes
Functional beta cell mass is an essential biomarker for the diagnosis and staging of diabetes. It has however proven technically challenging to study this parameter during diabetes progression. Here we have detailed the kinetics of the rapid decline in functional beta cell mass in the RIP-DTR mouse,...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2018
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| Online Access: | https://hdl.handle.net/10356/88140 http://hdl.handle.net/10220/45614 |
| _version_ | 1826119540392591360 |
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| author | van Krieken, Pim P. Dicker, Andrea Eriksson, Maria Herrera, Pedro L. Ahlgren, Ulf Berggren, Per-Olof Ilegems, Erwin |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) van Krieken, Pim P. Dicker, Andrea Eriksson, Maria Herrera, Pedro L. Ahlgren, Ulf Berggren, Per-Olof Ilegems, Erwin |
| author_sort | van Krieken, Pim P. |
| collection | NTU |
| description | Functional beta cell mass is an essential biomarker for the diagnosis and staging of diabetes. It has however proven technically challenging to study this parameter during diabetes progression. Here we have detailed the kinetics of the rapid decline in functional beta cell mass in the RIP-DTR mouse, a model of hyperglycemia resulting from diphtheria toxin induced beta cell ablation. A novel combination of imaging modalities was employed to study the pattern of beta cell destruction. Optical projection tomography of the pancreas and longitudinal in vivo confocal microscopy of islets transplanted into the anterior chamber of the eye allowed to investigate kinetics and tomographic location of beta cell mass decay in individual islets as well as at the entire islet population level. The correlation between beta cell mass and function was determined by complementary in vivo and ex vivo characterizations, demonstrating that beta cell function and glucose tolerance were impaired within the first two days following treatment when more than 50% of beta cell mass was remaining. Our results illustrate the importance of acquiring quantitative functional and morphological parameters to assess the functional status of the endocrine pancreas. |
| first_indexed | 2024-10-01T05:01:42Z |
| format | Journal Article |
| id | ntu-10356/88140 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:01:42Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/881402020-11-01T05:19:32Z Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes van Krieken, Pim P. Dicker, Andrea Eriksson, Maria Herrera, Pedro L. Ahlgren, Ulf Berggren, Per-Olof Ilegems, Erwin Lee Kong Chian School of Medicine (LKCMedicine) Beta Cell Diabetes DRNTU::Science::Medicine Functional beta cell mass is an essential biomarker for the diagnosis and staging of diabetes. It has however proven technically challenging to study this parameter during diabetes progression. Here we have detailed the kinetics of the rapid decline in functional beta cell mass in the RIP-DTR mouse, a model of hyperglycemia resulting from diphtheria toxin induced beta cell ablation. A novel combination of imaging modalities was employed to study the pattern of beta cell destruction. Optical projection tomography of the pancreas and longitudinal in vivo confocal microscopy of islets transplanted into the anterior chamber of the eye allowed to investigate kinetics and tomographic location of beta cell mass decay in individual islets as well as at the entire islet population level. The correlation between beta cell mass and function was determined by complementary in vivo and ex vivo characterizations, demonstrating that beta cell function and glucose tolerance were impaired within the first two days following treatment when more than 50% of beta cell mass was remaining. Our results illustrate the importance of acquiring quantitative functional and morphological parameters to assess the functional status of the endocrine pancreas. Published version 2018-08-20T04:23:12Z 2019-12-06T16:56:56Z 2018-08-20T04:23:12Z 2019-12-06T16:56:56Z 2017 Journal Article van Krieken, P. P., Dicker, A., Eriksson, M., Herrera, P. L., Ahlgren, U., Berggren, P.-O., & Ilegems, E. (2017). Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes. Scientific Reports, 7, 12440-. doi:10.1038/s41598-017-12124-w 2045-2322 https://hdl.handle.net/10356/88140 http://hdl.handle.net/10220/45614 10.1038/s41598-017-12124-w en Scientific Reports © 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. 10 p. application/pdf |
| spellingShingle | Beta Cell Diabetes DRNTU::Science::Medicine van Krieken, Pim P. Dicker, Andrea Eriksson, Maria Herrera, Pedro L. Ahlgren, Ulf Berggren, Per-Olof Ilegems, Erwin Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes |
| title | Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes |
| title_full | Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes |
| title_fullStr | Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes |
| title_full_unstemmed | Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes |
| title_short | Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes |
| title_sort | kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes |
| topic | Beta Cell Diabetes DRNTU::Science::Medicine |
| url | https://hdl.handle.net/10356/88140 http://hdl.handle.net/10220/45614 |
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