Β-Cell Ca2+ dynamics and function are compromised in aging. (January 2015)

• Record Type: Journal Article
• Authors: Barker, Christopher J.; Li, Luosheng; Köhler, Martin; Berggren, Per-Olof
• Is Part Of: Advances in biological regulation. Volume 57(2015)
• Page Start: 112
• Page End: 119
• Publication Date: 2015-01
• Subjects: Pancreatic beta cell -- Aging -- Calcium -- Calcium oscillations -- Insulin secretion -- Diabetes; Cellular control mechanisms -- Periodicals; Biological control systems -- Periodicals; Molecular biology -- Periodicals; Periodicals; 571.74
• DOI: 10.1016/j.jbior.2014.09.005
• Languages: English
• ISSNs: 2212-4926

Abstract

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 Ca 2+ concentration ([Ca 2+ ]i ) may be critical and that this is dependent on the proper function of the mitochondria. The [Ca 2+ ]i dynamics of the pancreatic β-cell are driven by an interplay between glucose-induced influx of extracellular Ca 2+ via voltage-dependent Ca 2+ channels and the inositol 1, 4, 5-trisphosphate (Ins(1, 4, 5) P 3 )-mediated liberation of Ca 2+ from intracellular stores. Our previous work has indicated a direct relationship between disruption of Ins(1, 4, 5) P 3 -mediated Ca 2+ regulation and loss of β-cell function, including disturbed [Ca 2+ ]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 [Ca 2+ ]i dynamics in mouse β-cells, particularly in the pattern of [Ca 2+ ]i oscillations. These changes are driven by modifications in both PLC/Ins(1, 4, 5) P 3 -mediated Ca 2+ mobilization from intracellular stores and decreased β-cell Ca 2+ 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.