Autoantibodies against CD38 (ADP-ribosyl cyclase/cyclic adp-ribose hydrolase) that impair glucose-induced insulin secretion in noninsulin- dependent diabetes patients

Fumiko Ikehata, Jo Satoh, Koji Nata, Akira Tohgo, Tetsuya Nakazawa, Ichiro Kato, Seiichi Kobayashi, Takako Akiyama, Shin Takasawa, Takayoshi Toyota, Hiroshi Okamoto

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

Cyclic ADP-ribose (cADPR) has been shown to be a mediator for intracellular Ca2+ mobilization for insulin secretion by glucose in pancreatic β cells, and CD38 shows both ADP-ribosyl cyclase to synthesize cADPR from NAD+ and cADPR hydrolase to hydrolyze cADPR to ADP-ribose. We show here that 13.8% of Japanese non-insulin-dependent diabetes (NIDDM) patients examined have autoantibodies against CD38 and that the sera containing anti-CD38 autoantibodies inhibit the ADP-ribosyl cyclase activity of CD38 (P ≤ 0.05). Insulin secretion from pancreatic islets by glucose is significantly inhibited by the addition of the NIDDM sera with anti-CD38 antibodies (P ≤ 0.04-0.0001), and the inhibition of insulin secretion is abolished by the addition of recombinant CD38 (P ≤ 0.02). The increase of cADPR levels in pancreatic islets by glucose was also inhibited by the addition of the sera (P ≤ 0.05). These results strongly suggest that the presence of anti-CD38 autoantibodies in NIDDM patients can be one of the major causes of impaired glucose-induced insulin secretion in NIDDM.

Original languageEnglish
Pages (from-to)395-401
Number of pages7
JournalJournal of Clinical Investigation
Volume102
Issue number2
DOIs
Publication statusPublished - 1998 Jul 15

Keywords

  • Ca mobilization
  • Islets
  • NAD
  • Second messenger
  • Western blot

ASJC Scopus subject areas

  • Medicine(all)

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