Effects of Azaserine and Nicotinamide on Insulin Release and Nicotinamide - Adenine Dinucleotide Metabolism in Isolated Rat Islets of Langerhans

1. The effects of azaserine and nicotinamide, agents which inhibit and stimulate hepatic NAD synthesis respectively, on the content of NAD+ and NADH in isolated rat islets of Langerhans incubated in vitro were studied. The effects of these compounds on the rates of insulin release, from isolated islets incubated in vitro, in response to various secretagogues were also measured. 2. Preincubation of islets in the presence of azaserine (0.3mM) caused a marked depletion of the normal islet-cell content of both NAD+ and NADH and prevented the secretion of insulin in response to stimulatory concentrations of D-glucose, xylitol, D-xylulose, L-arginine hydrochloride and L-leucine. 3. Preincubation of islets in the presence of nicotinamide (2mM) increased the islet content of NAD+ and enhanced the rate of release of insulin in response to D-glucose. Also when nicotinamide was present the inhibitory effect of azaserine on insulin release and the azaserine-induced depletion of the islet content ofNAD+ and NADH was prevented. 4. Preincubation with azaserine was without effect on the stimulation of insulin release caused by theophylline or dibutyryl cyclic AMP. 5. It is suggested that insulin release caused by sugars and amino acids is dependent on the maintenance ofNAD concentrations, though this may not be the case for release due to theophylline and dibutyryl cyclic AMP.