Normalization of hepatic lysosomal autophagy in streptozotocin diabetic rats after pancreatic transplantation.

This study was performed to determine whether the enhanced hepatic autophagocytosis occurring in diabetes mellitus could be reversed by pancreatic transplantation despite the persistence of hyperglucagonemia in transplant recipients. Twenty weeks after pancreatic transplantation, hepatic lysosomes and autophagic vacuoles were quantitated morphometrically in untreated streptozotocin-diabetic rats and in streptozotocin-diabetic rats treated by pancreatic transplantation. Hyperglycemia and hypoinsulinemia in untreated diabetic rats were corrected after pancreatic transplantation. However, the peripheral plasma glucagon concentration remained significantly higher in transplant recipients than in non-diabetic controls. Light microscopic morphometry revealed no significant effect of the diabetic state or its reversal on the volume of the single hepatocyte or the volume density and numerical density of hepatocytes. However, electron microscopic examination showed that the number and volume density of lysosomes and autophagic vacuoles, which were significantly increased in diabetic rats, returned to control values after pancreatic transplantation. It is concluded that chronic hyperglucagonemia does not preserve enhanced hepatic autophagocytosis when the diabetic hypoinsulinemia is corrected by the pancreatic transplant.