Cyclic ADP-ribose and inositol 1,4,5-trisphosphate as alternate second messengers for intracellular Ca2+ mobilization in normal and diabetic β- cells

Shin Takasawa, Takako Akiyama, Koji Nata, Michio Kuroki, Akira Tohgo, Naoya Noguchi, Seiichi Kobayashi, Ichiro Kato, Toshiaki Katada, Hiroshi Okamoto

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99 Citations (Scopus)

Abstract

Intracellular Ca2+ mobilization occurs in a variety of cellular processes and is mediated by two major systems, the inositol 1,4,5- trisphosphate (IP3) and cyclic ADP-ribose (cADPR) systems. cADPR has been proposed to be a second messenger for insulin secretion induced by glucose in pancreatic β-cells (Takasawa, S., Nata, K., Yonekura, H., and Okamoto, H. (1993) Science 259, 370373). Here we show that the cADPR signal system for insulin secretion is replaced by the IP3 system in diabetic β-cells such as ob/ob mouse islets and RINm5F cells. We measured the cADPR content in these β-cells by radioimmunoassay and found that the increase of the cADPR content by glucose did not occur in ob/ob mouse islets and RINm5F cells, whereas the increased cADPR level by glucose was observed in normal rat and mouse islets. Microsomes of these diabetic β-cells released Ca2+ in response to IP3 but not to cADPR. In the diabetic β-cells, CD38 (ADP-ribosyl cyclase/cADPR hydrolase) and type 2 ryanodine receptor mRNAs were scarcely detected and, in contrast, an increased expression of IP3 receptor mRNAs was observed. The diabetic β-cells secreted insulin rather by carbamylcholine than by glucose.

Original languageEnglish
Pages (from-to)2497-2500
Number of pages4
JournalJournal of Biological Chemistry
Volume273
Issue number5
DOIs
Publication statusPublished - 1998 Jan 30

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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