Cyclic ADP-Ribose in Insulin Secretion from Pancreatic βCells

• DOI: 10.1126/science.8420005
• Publication Date: 2006-10-05T23:05:09Z
• Authors: Shin Takasawa; Koji Nata; Hideto Yonekura; Hiroshi Okamoto
• Keywords: Male; Niacinamide; Adenosine Diphosphate Ribose; Cyclic ADP-Ribose; 0303 health sciences; Dose-Response Relationship, Drug; Heparin; Inositol 1,4,5-Trisphosphate; Poly(ADP-ribose) Polymerase Inhibitors; Second Messenger Systems; Rats; 3. Good health; Islets of Langerhans; 03 medical and health sciences; Glucose; Cerebellum; Microsomes; Benzamides; Insulin Secretion; Animals; Insulin; Calcium; Rats, Wistar

Inositol 1,4,5-trisphosphate (IP 3 ) 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 IP 3 , 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.