The CD38-Cyclic ADP-Ribose Signal System in Pancreatic ß-Cells

The Discovery and Biological Significance of a Novel Signal System in Mammalian Cells


In the early 1980’s, we showed that maintenance of the cellular NAD+ level in β-cells of the islets of Langerhans is essential for the synthesis and secretion of insulin, and proposed a unifying model for the action of the diabetogenic agents alloxan and streptozotocin on pancreatic β-cells (Figure 1) [1–10]. Central to the model are breaks in the nuclear DNA of β-cells, resulting from either an accumulation of free radicals or from the alkylation of DNA. These breaks induce DNA repair involving the activation of poly(ADP-ribose) synthetase/polymerase (PARP), which uses cellular NAD+ as a substrate. As a result, the intracellular levels of NAD+ fall dramatically, which leads to energy depletion and the inhibition of cellular functions including insulin synthesis and secretion, and thus the β-cell ultimately dies.


Insulin Secretion Pancreatic Islet Ryanodine Receptor PARP Inhibitor Glucose Stimulation 
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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  1. 1.Department of BiochemistryTohoku University Graduate School of MedicineMiyagiJapan

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