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https://hdl.handle.net/10356/103782
Title: | Defects in β-cell Ca2+ dynamics in age-induced diabetes | Authors: | Li, Luosheng Trifunovic, Aleksandra Köhler, Martin Wang, Yixin Petrovic Berglund, Jelena Illies, Christopher Juntti-Berggren, Lisa Larsson, Nils-Göran Berggren, Per-Olof |
Keywords: | DRNTU::Science::Medicine | Issue Date: | 2014 | Source: | Li, L., Trifunovic, A., Köhler, M., Wang, Y., Petrovic Berglund, J., Illies, C., et al. (2014). Defects in β-cell Ca2+ dynamics in age-induced diabetes. Diabetes, 63(12), 4100-4114. | Series/Report no.: | Diabetes | Abstract: | Little is known about the molecular mechanisms underlying age-dependent deterioration in β-cell function. We now demonstrate that age-dependent impairment in insulin release, and thereby glucose homeostasis, is associated with subtle changes in Ca2+ dynamics in mouse β-cells. We show that these changes are likely to be accounted for by impaired mitochondrial function and to involve phospholipase C/inositol 1,4,5-trisphosphate–mediated Ca2+ mobilization from intracellular stores as well as decreased β-cell Ca2+ influx over the plasma membrane. We use three mouse models, namely, a premature aging phenotype, a mature aging phenotype, and an aging-resistant phenotype. Premature aging is studied in a genetically modified mouse model with an age-dependent accumulation of mitochondrial DNA mutations. Mature aging is studied in the C57BL/6 mouse, whereas the 129 mouse represents a model that is more resistant to age-induced deterioration. Our data suggest that aging is associated with a progressive decline in β-cell mitochondrial function that negatively impacts on the fine tuning of Ca2+ dynamics. This is conceptually important since it emphasizes that even relatively modest changes in β-cell signal transduction over time lead to compromised insulin release and a diabetic phenotype. | URI: | https://hdl.handle.net/10356/103782 http://hdl.handle.net/10220/24587 |
DOI: | 10.2337/db13-1855 | Schools: | Lee Kong Chian School of Medicine (LKCMedicine) | Rights: | © 2014 American Diabetes Association. This is the author created version of a work that has been peer reviewed and accepted for publication by Diabetes, American Diabetes Association. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.2337/db13-1855]. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | LKCMedicine Journal Articles |
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Defects in beta-cell Ca2+ dynamics in age-induced diabetes.pdf | Main article | 2.5 MB | Adobe PDF | View/Open |
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