Cyclic ADP-ribose in insulin secretion from pancreatic β cells

Shin Takasawa, Koji Nata, Hideto Yonekura, Hiroshi Okamoto

Research output: Contribution to journalArticlepeer-review

390 Citations (Scopus)

Abstract

Inositol 1,4,5-trisphosphate (IP3) is thought to be a second messenger for intracellular calcium mobilization. However, in a cell-free system of islet microsomes, cyclic adenosine diphosphate-ribose (cADP-ribose), a nicotinamide adenine dinucleotide (NAD+) metabolite, but not IP 3, induced calcium release. In digitonin-permeabilized islets, cADP-ribose and calcium, but not IP3, induced insulin secretion. Islet microsomes released calcium when combined with the extract from intact islets that had been incubated with high concentrations of glucose. Sequential additions of cADP-ribose inhibited the calcium release response to extracts from islets treated with high concentrations of glucose. Conversely, repeated additions of the islet extract inhibited the calcium release response to a subsequent addition of cADP-ribose. These results suggest that cADP-ribose is a mediator of calcium release from islet microsomes and may be generated in islets by glucose stimulation, serving as a second messenger for calcium mobilization in the endoplasmic reticulum.

Original languageEnglish
Pages (from-to)370-373
Number of pages4
JournalScience
Volume259
Issue number5093
DOIs
Publication statusPublished - 1993

ASJC Scopus subject areas

  • General

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