The CD38-cyclic ADP-ribose signaling system in insulin secretion

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32 Citations (Scopus)


Glucose induces an increase in the intracellular Ca2+ concentration in pancreatic β-cells to secrete insulin. CD38 occurs in β-cells and has both ADP-ribosyl cyclase, which catalyzes the formation of cyclic ADP-ribose (cADPR) from NAD+, and cADPR hydrolase, which converts cADPR to ADP-ribose. ATP, produced by glucose metabolism, competes with cADPR for the binding site, Lys-129, of CD38, resulting in the inhibition of the hydrolysis of cADPR and thereby causing cADPR accumulation in β-cells. Cyclic ADP-ribose then binds to FK506-binding protein 12.6 is the ryanodine receptor Ca2+ channel (RyR), dissociating the binding protein from RyR to induce the release of Ca2+ from the endoplasmic reticulum. Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) phosphorylates RyR to sensitize and activate the Ca2+ channel. Ca2+, released from the RyR, further activates CaM kinase II and amplifies the process. Thus, cADPR acts as a second messenger for Ca2+ mobilization to secrete insulin. The novel mechanism of insulin secretion described above is different from the conventional hypothesis in which Ca2+ influx from extracellular sources plays a role in insulin secretion by glucose.

Original languageEnglish
Pages (from-to)115-118
Number of pages4
JournalMolecular and Cellular Biochemistry
Issue number1-2
Publication statusPublished - 1999 Apr 24


  • CD38
  • Ca/calmodulin-dependent protein kinase II
  • Cyclic ADP-ribose
  • Diabetes
  • FK506-binding protein
  • Insulin
  • Ryanodine receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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