High dose nicotinamide fails to prevent diabetes in BB rats.
Nicotinamide which is an inhibitor of poly (ADPR) synthetase and precursor of NAD has been observed to prevent diabetes in some experimental models possibly by protecting beta cells. To determine whether nicotinamide could cure or prevent type 1 diabetes, we administered large doses (0.5 g/Kg/d) to BB rats. When used in the 45 days following diagnosis nicotinamide failed to bring remission. As a preventive treatment, nicotinamide administered between the 40th and 90th day of age, alone or in association with desferrioxamine did not significantly lower the incidence of diabetes (23% and 30.8% respectively vs. 56.6%). When used earlier, immediately after weaning, nicotinamide did not affect the incidence of diabetes in this model (62.5%). The degree of protection was not comparable with that obtained with cyclosporin A (15% of diabetic animals). Histology study of the pancreas from the animals killed either immediately or 1 year after treatment revealed no endocrine tumor. These findings suggest that in BB rats nicotinamide has little or no effect on the course of autoimmune diabetes mellitus thus dampening the high hopes for this drug in the treatment of human diabetes.
Hermitte
L
L
Laboratory of Diabetology, La Timone Hospital, University of Marseille, France.
Vialettes
B
B
Atlef
N
N
Payan
M J
MJ
Doll
N
N
Scheimann
A
A
Vague
P
P
D000367:Age Factors; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001786:Blood Glucose / Q000032:analysis; D016572:Cyclosporine / Q000627:therapeutic use; D004249:DNA Damage; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D006965:Hyperplasia; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D011913:Rats, Inbred BB
D001786:Blood Glucose; D007328:Insulin; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D009536:Niacinamide; D016572:Cyclosporine; D003676:Deferoxamine