Pyridine Nucleotide Depletion in Pancreatic Islets Associated with Streptozotocin-induced Diabetes

Abstract

An investigation of NAD-NADH concentrations in the pancreatic islets of rats following diabetogenic doses (65 mg./kg.) of streptozotocin (SZ), given singly or in combination with nicotinamide or nicotinic acid, is reported. After a given treatment of the animals, the pancreases were surgically removed. The concentrations of NAD and NADH were determined on islets isolated from freeze-dried sections of the pancreas. In the pancreatic islets of untreated control animals, the mean ± S.E. concentrations of NAD and NADU were 1,122 ± 5 7 and 129 ± 28 mμnmoles/gm. dry tissue, respectively. The NAD content of the islets decreased to 27 per cent of the control value one hour and to 12 per cent five hours after administration of SZ. NADH concentration five hours after SZ was significantly reduced from the control value. When nicotinamide was given thirty minutes before SZ, the depletion of NAD associated with SZ administration was prevented. When nicotinamide was given one hour after SZ, the depressed NAD concentration observed at this time was subsequently raised. In contrast, nicotinic acid given thirty minutes prior to SZ did not prevent depletion of NAD. The data suggest that streptozotocin-induced betacell deterioration may be etiologically related to depletion of cellular NAD.