Protective effect of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, against streptozotocin-induced diabetes.
The addition of 3-aminobenzamide (a potent inhibitor of poly(ADP-ribose)synthetase) into the incubation medium, prevents streptozotocin-induced inhibition of glucose-stimulated insulin release from isolated islets [control 142 +/- 14 microU X islet-1 X h-1; streptozotocin (0.5 mg/ml) 31 +/- 8; 3-aminobenzamide (1.0 mg/ml) 96 +/- 11; streptozotocin plus 3-aminobenzamide 122 +/- 19]. In vivo, intraperitoneal 3-aminobenzamide 300 mg/kg body weight prevents the appearance of overt diabetes in streptozotocin-treated rats. These protective effects of 3-aminobenzamide are dose-dependent and are similar to those exerted by nicotinamide. Taking into account that poly ADP-ribosylation is involved in the repair of damaged DNA, the protection exerted by 3-aminobenzamide against the diabetogenic effect of streptozotocin strongly supports the view that this acute effect may be a major consequence of the activation of DNA repair mechanisms in islet cells.
Masiello
P
P
Cubeddu
T L
TL
Frosina
G
G
Bergamini
E
E
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009536:Niacinamide / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D001549:Benzamides; D001786:Blood Glucose; D007328:Insulin; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009536:Niacinamide; D013311:Streptozocin; C025160:3-aminobenzamide