Defects in β-cell Ca2+ dynamics in age-induced diabetes

Luosheng Li, Aleksandra Trifunovic, Martin Köhler, Yixin Wang, Jelena Petrovic Berglund, Christopher Illies, Lisa Juntti-Berggren, Nils Göran Larsson, Per Olof Berggren

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Little is known about the molecular mechanisms underlying age-dependent deterioration in b-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 agedependent 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.

Original languageEnglish (US)
Pages (from-to)4100-4114
Number of pages15
JournalDiabetes
Volume63
Issue number12
DOIs
StatePublished - Dec 1 2014

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Li, L., Trifunovic, A., Köhler, M., Wang, Y., Berglund, J. P., Illies, C., Juntti-Berggren, L., Larsson, N. G., & Berggren, P. O. (2014). Defects in β-cell Ca2+ dynamics in age-induced diabetes. Diabetes, 63(12), 4100-4114. https://doi.org/10.2337/db13-1855