The characterization of the protection by nicotinamide against the action of diabetogenic nitrosoureas.
The ability of various amide compounds to reverse the inhibitory effects of diabetogenic nitrosoureas on glucose stimulated insulin secretion was ascertained in isolated islets of Langerhans. Addition of nicotinamide 30 or more minutes after exposure of islets to streptozotocin (STZ) did not significantly reverse the insulinlytic effect of STZ. Not only nicotinamide isomers--isonicotinamide and picolinamide, but also other primary amides--pyrazinamide and benzamide were equally as effective as nicotinamide against nitrosourea and alloxan induced beta cytotoxicity. The protective ability of the amides was dose dependent in all cases and ranged from over 90% for 20 mM, 70% for 10 mM and 26% for 5 mM regardless of which isomer was used. The stronger the basicity of the ring nitrogen of pyridine derivative, the more potent the amide in protecting islets against the effect of either STZ or MNU. We have presented evidence to show that the protective ability of nicotinamide against diabetogenic nitrousoureas is not a specific property of nicotinamide but rather such action is shared by amides with stronger basic pyridine nucleus.
Akpan
J O
JO
Department of pharmacology and toxicology Indiana University School of Medicine, Indianapolis.
D000818:Animals; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D013311:Streptozocin / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007328:Insulin; D009536:Niacinamide; D013311:Streptozocin; D005947:Glucose