Pancreas from mice treated with 500 ing. per kilogram of nicotinamide intraperitoneally fifteen minutes before 200 nig. per kilogram of streptozotocin intravenously showed mostly unaltered islet B cells after eight, eighteen or fortyeight hours. Mice pretreated with 1,500 mg. per kilogram of either NAD, NADP or NADPH intraperitoneally showed almost no B cell lesions at eight hours. At eighteen hours some B cell necrohiosis was observed but of lesser extent than that seen after streptozotocin alone at eight hours. At forty-eight hours B cells showed diffuse, uniform necrobiosis only slightly less extensive than that seen in the group treated with streptozotocin alone.

Pretreatment of mice with 500 mg. per kilogram nicotinamide intraperitoneally fifteen minutes before 100 mg. per kilogram alloxan intravenously failed to alter the extent of islet B cell lesions at eighteen hours. When the dosage of nicotinamide administered was increased to 1,000 mg. per kilogram and the time of pretreatment at this dose level increased to sixty minutes there was a slight decrease in the extent of B cell necrosis. Islets from rats pretreated with 1,000 mg. per kilogram nicotinamide intravenously sixty minutes prior to alloxan also showed a general lack of protective influence. Under the same conditions nicotinamide completely protected rats against the B cell cytotoxicity of streptozotocin.

These findings demonstrate the almost specific protective action of nicotinamide against streptozotocin-induced B cell necrosis. While pyridine nucleotides slowed its development they did not prevent B cell necrosis after streptozotocin. The dissimilarity in the action of nicotinamide and pyridine nucleotides makes doubtful the view that streptozotocin-induced B cell necrosis is mediated via lowering of cellular content of NAD or other pyridine nucleotides below critical levels. The minimal protection afforded by nicotinamide against alloxan-induced B cell necrosis, as contrasted with its effectiveness against streptozotocin, confirms the view that the basic mechanisms of action of these drugs are different despite comparable selective B cell cytotoxicity.

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