β-Cell Ca2+ dynamics and function are compromised in aging

Christopher J. Barker, Luosheng Li, Martin Köhler, Per Olof Berggren

Research output: Contribution to journalReview article

9 Scopus citations

Abstract

Defects in pancreatic β-cell function and survival are key components in type 2 diabetes (T2D). An age-dependent deterioration in β-cell function has also been observed, but little is known about the molecular mechanisms behind this phenomenon. Our previous studies indicate that the regulation of cytoplasmic free Ca2+ concentration ([Ca2+]i) may be critical and that this is dependent on the proper function of the mitochondria. The [Ca2+]i dynamics of the pancreatic β-cell are driven by an interplay between glucose-induced influx of extracellular Ca2+ via voltage-dependent Ca2+ channels and the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-mediated liberation of Ca2+ from intracellular stores. Our previous workhas indicated a direct relationship between disruption of Ins(1,4,5)P3-mediated Ca2+ regulation and loss of β-cell function, including disturbed [Ca2+]i dynamics and compromised insulin secretion. To investigate these processes in aging we used three mouse models, a premature aging mitochondrial mutator mouse, a mature aging phenotype (C57BL/6) and an aging-resistant phenotype (129). Our data suggest that age-dependent impairment in mitochondrial function leads to modest changes in [Ca2+]i dynamics in mouse β-cells, particularly in the pattern of [Ca2+]i oscillations. These changes are driven by modifications in both PLC/Ins(1,4,5)P3-mediated Ca2+ mobilization from intracellular stores and decreased β-cell Ca2+ influx over the plasma membrane. Our findings underscore an important concept, namely that even relatively small, time-dependent changes in β-cell signal-transduction result in compromised insulin release and in a diabetic phenotype.

Original languageEnglish (US)
Pages (from-to)112-119
Number of pages8
JournalAdvances in Biological Regulation
Volume57
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Aging
  • Calcium
  • Calcium oscillations
  • Diabetes
  • Insulin secretion
  • Pancreatic beta cell

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology
  • Molecular Medicine

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