An electron microscopic and biochemical study of the effects of glucagon on glycogen autophagy in the liver and heart of newborn rats

Abstract

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.

Electron microscopic and biochemical study of the effects of rapamycin on glycogen autophagy in the newborn rat liver

“…Thus, the hydrolytic degradation assists the phosphorolytic degradation of glycogen in producing glucose (Rosenfeld, 1964;Pfeifer, 1970;Thys, 1970;Shelburne et al, 1973;Glaumann et al, 1985). cAMP and cAMP-elevating agents such as glucagon promote the sequestrational step of hepatocytic autophagy and increase the lysosomal glycogen-hydrolyzing (but not the maltose-hydrolyzing) activity of acid glucosidase, whereas cAMP-antagonizing agents such as propranolol or insulin had opposite results (Kotoulas, 1981(Kotoulas, , 1984(Kotoulas, , 1986Kotoulas et al, 1991Kotoulas et al, , 2003Kalamidas et al, 1994;Holen, 1996;Kalamidas and Kotoulas, 2000b;Kondomerkos et al, 2004).…”

“…cAMP or cAMP-dependent protein kinase, which induce autophagy, have been found to exert a stimulatory effect on PP2A activity, counteracting the inhibitory effect of insulin Ragolia, 1996, 1999;Usui et al, 1998;Cutler et al, 1999;Hartley and Cooper, 2002;Feschenko et al, 2002;Moon and Lerner, 2003). Preliminary experiments showed that cAMP-elevating glucagon, which induces glycogen autophagy (Kondomerkos et al, 2004), caused an increase in the 10 nM okadaic acid-inhibitable casein phosphatase (including PP2A or PP2A-like) activity (control: 85 Ϯ 37 nmol P i liberated/ hr/mg protein; glucagon: 523 Ϯ 203 nmol P i liberated/ hr/mg protein; P Ͻ 0.05, n ϭ 4). This observation supports the view expressed by others that the cAMP and mTOR pathways appear to play parallel roles and converge to the regulation of autophagy and other processes Peterson et al, 1999;Feschenko et al, 2002;Xia et al, 2003).…”

“…cAMP-elevating agents induce certain aspects of autophagy such as increased fractional volume of autophagic vacuoles, lysosomal glycogen-hydrolyzing alpha glucosidase activity, and breakdown of glycogen inside the autophagic vacuoles. These effects depend, at least in part, on de novo protein synthesis (Kotoulas, 1984(Kotoulas, , 1986(Kotoulas, , 1988Kalamidas et al, 1994;Kondomerkos et al, 2004).…”

“…Glycogen autophagy, including the formation of glycogencontaining autophagosomes and the hydrolytic degradation of polysaccharide in autolysosomes, appears to be a selective process under conditions of demand for the production of glucose, such as in newborn animals (Rosenfeld, 1964;Kotoulas et al, 1991;Kalamidas and Kotoulas, 2000b;Kondomerkos et al, 2004).…”

Myocardial stress and autophagy: mechanisms and potential therapies

“…In the neonatal heart, elevated acid α-glucosidase activity and visualization of glycogen in autophagic vacuoles by electron microscopy is observed during the postnatal period of nutrient deprivation. 50, 51 More detailed dissection of the cardiomyocyte regulatory pathways of insulin signaling, glucose response and glycophagy induction is required.…”