Intracellular calcium ion response to glucose in β-cells of calbindin-D 28k nullmutant mice and in βHC13 cells overexpressing calbindin-D 28k

J. Parkash, M. A. Chaudhry, A. S. Amer, S. Christakos, W. B. Rhoten

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Abstract

This article describes studies on the glucose-induced responses of intracellular Ca 2+ concentration ([Ca 2+] i), insulin release, and redistribution of calbindin-D 28k, a calcium-binding regulatory protein, in β-cells of pancreatic islets of calbindin-D 28k knockout (KO) and wildtype mice (C57BL6) as well as in βHC-13 control cells and βHC-13 CaBP40 cells (β-cell line overexpressing calbindin-D 28k). Upon increasing the glucose concentration from 2.8 to 30 mM, islets of KO mice showed a significantly greater increase in [Ca 2+] i (mean increase in [Ca 2+] i, i.e., Δ[Ca 2+] i, was 296 nM) compared with wild-type mice (Δ[Ca 2+] i = 97 nM). βHC-13 CaBP40 cells showed little change in [Ca 2+] i upon elevation of glucose from 5.5 to 32.7 mM, whereas βHC-13 control cells exhibited significant increases in [Ca 2+] i (Δ[Ca 2+] i = 510 nM). Similarly, upon addition of 30 mM glucose, the rate of insulin release increased from 25.2 (basal rate) to 145.2 pg/mL/min in βHC-13 control cells, whereas in βHC-13 CaBP40 cells the rate of insulin release was only 27.5 pg/mL/min in high glucose. Thus, levels of calbindin-D 28k in β-cells affect both [Ca 2+] i and insulin secretion in response to glucose. The three-dimensional reconstruct of confocal immunofluorescent images showed that glucose caused redistribution of calbindin-D 28k resulting in co-localization in the region of L-type voltage-dependent calcium channels (VDCC). This colocalization may be an important regulatory function concerning Ca 2+ influx via L-type VDCC and exocytosis of insulin granules.

Original languageEnglish (US)
Pages (from-to)221-229
Number of pages9
JournalEndocrine
Volume18
Issue number3
DOIs
StatePublished - Aug 2002

All Science Journal Classification (ASJC) codes

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Keywords

  • Calbindin-D
  • Insulin
  • Intracellular Ca
  • Islets
  • Knockout mouse
  • β-cells

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