Cyclic ADP-ribose-mediated insulin secretion and Reg, regenerating gene

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Glucose is the primary stimulus of insulin secretion in pancreatic β- cells of the islets of Langerhans. CD38 has both ADP-ribosyl cyclase, which catalyzes the formation of cyclic ADP-ribose from NAD+, and cyclic ADP- ribose hydrolase, which converts cyclic ADP-ribose to ADP-ribose. ATP, produced by glucose metabolism, inhibits the cyclic ADP-ribose hydrolase of CD38 and therefore causes cyclic ADP-ribose accumulation in β-cells. Then, cyclic ADP-ribose acts as a second messenger for Ca2+ mobilization from the endoplasmic reticulum to secrete insulin. The mechanism of insulin secretion as described above is completely different from the conventional hypothesis in which Ca2+ influx from extracellular sources was assumed to play a role in insulin secretion by glucose. On the other hand, strategies for influencing the replication of islet β-cells and the growth of the β-cell mass may be more important for ameliorating diabetes. Reg, regenerating gene, is involved in the growth of the β-cell mass, and Reg protein has been shown to increase the β-cell mass in a 90% depancreatized diabetic rat model, thereby ameliorating the diabetes. CD38 is involved in the formation of cyclic ADP-ribose and is essential for the glucose sensitivity of β-cells for insulin secretion. Therefore, CD38 gene and Reg gene will become targets for genetic engineering for diabetic β-cells.

Original languageEnglish
Pages (from-to)74-78
Number of pages5
JournalJournal of Molecular Medicine
Issue number1
Publication statusPublished - 1999


  • CD38
  • Cyclic ADP-ribose
  • Insulin secretion
  • Reg
  • The OKAMOTO model


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