Insulin exocytosis and glucose-mediated increase in cytoplasmic free Ca 2+ concentration in the pancreatic β-cell are independent of cyclic ADP-ribose

Dominic Luc Webb, Md Shahidul Islam, Alexandre M. Efanov, Graham Brown, Martin Köhler, Olof Larsson, Per Olof Berggren

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Stimulation of pancreatic β-cells by glucose gives rise to an increase in the cytoplasmic free calcium concentration ([Ca 2+](i)) and exocytosis of insulin. Cyclic adenosine 5'-diphosphate ribose (cADPR), a metabolite of β-NAD +, has been reported to increase [Ca 2+](i) in pancreatic β-cells by releasing Ca 2+ from inositol 1,4,5-trisphosphate-insensitive intracellular stores. In the present study, we have examined the role of cADPR in glucose-mediated increases in [Ca 2+](i) and insulin exocytosis. Dispersed ob/ob mouse β-cell aggregates were either pressure microinjected with fura-2 salt or loaded with fura-2 acetoxymethyl ester, and [Ca 2+](i) was monitored by microfluorimetry. Microinjection of β-NAD + into fura-2- loaded β-cells did not increase [Ca 2+](i) nor did it alter the cells' subsequent [Ca 2+](i) response to glucose. Cells microinjected with the cADPR antagonist 8NH 2-cADPR increased [Ca 2+](i) in response to glucose equally well as those injected with cADPR. Finally, the ability of cADPR to promote exocytosis of insulin in electropermeabilized β-cells was investigated. cADPR on its own did not increase insulin secretion nor did it potentiate Ca 2+-induced insulin secretion. We conclude that cADPR neither plays a significant role in glucose-mediated increases in [Ca 2+](i) nor interacts directly with the molecular mechanisms regulating exocytosis of insulin in normal pancreatic β-cells.

Original languageEnglish (US)
Pages (from-to)19074-19079
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number32
DOIs
StatePublished - Aug 27 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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