Long-term effects of exposure of pancreatic islets to nicotinamide in vitro on DNA synthesis, metabolism and B-cell function.
Using 3H-thymidine labeling techniques, we found that rates of DNA synthesis in islet cells doubled when mouse pancreatic islets were cultured for 1 week with 10 mmol/l nicotinamide, a potent poly(ADP-ribose) synthetase inhibitor. Culture with nicotinamide partially inhibited glucose-stimulated insulin release, whereas the islet insulin content and rate of (pro)insulin biosynthesis remained unchanged. Long-term exposure to nicotinamide decreased glucose oxidation and ATP content in the islets. The findings support the view that poly(ADP-ribose)synthetase inhibitors stimulate islet cell replication, but may be accompanied by significant inhibitory effects on islet cell function.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009243:NAD / Q000032:analysis; D009536:Niacinamide / Q000494:pharmacology*; D010084:Oxidation-Reduction; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D007328:Insulin; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D009536:Niacinamide; D000255:Adenosine Triphosphate; D004247:DNA; D005947:Glucose