Diurnal variability of cysteine and glutathione content in the pancreas and liver of the mouse

Abstract

The sensitivity of organs such as the liver to injury by certain drugs is modulated by the endogenous capacity to synthesize glutathione during periods of increased demand. Recent experimental evidence suggests that glutathione availability could also play an important role in preventing pancreatic injury as well. To better understand the role of cysteine availability in regulating glutathione homeostasis in the pancreas and liver under normal conditions, the diurnal variation in cysteine in mouse pancreas and liver was measured and compared with corresponding 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. Fasting prevented this diurnal variation in pancreatic cysteine. Pancreatic glutathione was at its lowest at 10 P.M. and rose sharply to a peak at 2 A.M. Fasting had no effect on this diurnal pattern. In contrast to the pancreas, fasting did not prevent the diurnal change in liver cysteine, whereas it caused substantial depletion of liver glutathione. Together, these findings suggest that under normal conditions, pancreatic and liver glutathione content are not determined solely by tissue cysteine availability. Moreover, basal glutathione content is under differing homeostatic mechanisms in the pancreas and the liver.