DIURNAL VARIABILITY OF CYSTEINE AND GLUTATHIONE CONTENT IN THE PANCREAS AND LIVER OF THE MOUSE

The sensitivity of organs such as the liver to injury by certain drugs is modulated by the endogenous capacity to synthesize glutathione dur ing periods of increased demand. Recent experimental evidence suggests that glutathione availability could also play an important role in pr eventing pancreatic injury as well. To better understand the role of c ysteine availability in regulating glutathione homeostasis in the panc reas and liver under normal conditions, the diurnal variation in cyste ine in mouse pancreas and liver was measured and compared with corresp onding measurements of organ glutathione content. Pancreatic cysteine varied significantly over a 24-hr period, dropping to 21 nmol/g at 2 P .M. and rising to 68 nmol/g at 10 P.M. Pasting prevented this diurnal variation in pancreatic cysteine. Pancreatic glutathione was at its Lo west at 10 P.M. and rose sharply to a peak at 2 A.M. Fasting had no ef fect on this diurnal pattern. In contrast to the pancreas, fasting did not prevent the diurnal change in liver cysteine, whereas it caused s ubstantial depletion of liver glutathione. Together, these findings su ggest that under normal conditions, pancreatic and liver glutathione c ontent are not determined solely by tissue cysteine availability. More over, basal glutathione content is under differing homeostatic mechani sms in the pancreas and the liver.