No abstract

Glycogen autophagy, which includes the sequestration and degradation of cell glycogen in the autophagic vacuoles, is a selective process under conditions of demand for the massive hepatic production of glucose, as in the postnatal period. It represents a link between autophagy and glycogen metabolism. The formation of autophagic vacuoles in the hepatocytes of newborn animals is spatially and biochemically related to the degradation of cell glycogen. Many molecular elements and signaling pathways including the cyclic AMP/cyclic AMP-dependent protein kinase and the phosphoinositides/TOR pathways are implicated in the control of this process. These two pathways may converge on the same target to regulate glycogen autophagy.

The effects of glucagon on the ultrastructural appearance and acid glucosidase activities in the liver and heart of newborn rats were studied. Liver or heart glycogen-hydrolyzing activity of acid glucosidase increased 3 hours after birth and gradually decreased from 3 to 9 hours. Maltose-hydrolyzing activity of acid glucosidase also rose 3 hours after birth, maintained a plateau between 3 and 6 hours, and fell at 9 hours. The administration of glucagon increased autophagic activity in the hepatocytes at the age of 6 hours. Glycogen inside the autophagic vacuoles was decreased, apparently due to the increased glycogen degradation. Glycogen-hydrolyzing activity was elevated in both the liver and the heart. Maltose-hydrolyzing activity was elevated in the liver, but not in the heart. The results of this study suggest that the glycogen-hydrolyzing and maltose-hydrolyzing activities of acid glucosidase are due to different enzymes. Glucagon's effect on the glycogen-hydrolyzing acid glucosidase activity and autophagosomal morphology is similar in both the liver and the heart.

The effects of rapamycin on glycogen autophagy in the newborn rat liver were studied using biochemical determinations, electron microscopy, and morphometric analysis. Rapamycin increased the fractional volume of hepatocytic autophagic vacuoles, the liver lysosomal glycogen-hydrolyzing activity of acid glucosidase, the degradation of glycogen inside the autophagic vacuoles, and decreased the activity of acid mannose 6-phosphatase. These findings suggest that rapamycin, a known inhibitor of the mammalian target of rapamycin (mTOR) signaling, induces glycogen autophagy in the newborn rat hepatocytes. mTOR may participate in the regulation of this process.

The effects of the administration of parenteral glucose on the postnatal glycogen autophagic activity and its relationship to the general autophagic activity, were studied in newborn rat liver using electron microscopy and biochemical methods. Glucose abolished the normal postnatal hypoglycemia and preserved the hepatocytic hyaloplasmic glycogen to the levels of birth. It also inhibited the normal postnatal increase in the number and volume of autophagic vacuoles. Glucose especially decreased the rate of postnatal development of the glycogen-containing autophagic vacuoles. This decrease was greater than that of the autophagic vacuoles in general. In the control animals at the age of 6 h, the total volume of the glycogen-containing autophagic vacuoles accounted for 87% of the autophagic vacuoles in general, whereas in the glucose-treated animals of the same age, for only 62%. The results of this and previous studies support the view that the general autophagic activity that develops in the immediate postnatal period in rat hepatocytes is mainly expressed as glycogen autophagic activity selectively inhibited by glucose.