Autophagosomal glycogen‐degrading activity and its relationship to the general autophagic activity in newborn rat hepatocytes: The effects of parenteral glucose administration

Abstract

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.

The administration of nonmetabolizable glucose analogues fails to suppress the development of glycogen autophagy in newborn rat hepatocytes

“…95649) were from Fluka (Athens, Greece). D ‐Glucose, 3MG, and propranolol hydrochloride 1 mg/mL ready solution (Inderal) were obtained as before (Kalamidas and Kondomerkos,2010; Kondomerkos et al,2004).…”

“…The liver glycogen‐hydrolyzing activity of acid α‐1,4‐glucosidase is also inhibited, and the hepatocytic autophagic vacuoles show increased amounts of undigested glycogen evidently due to the impaired glycogen autophagic activity (Kalamidas et al,1994; Kondomerkos et al,2005; Kotoulas et al,1971,2004). In a previous study, preliminary evidence suggested that the inhibitory effect of glucose on acid glucosidase depended, at least partly, on glucose phosphorylation (Kalamidas and Kondomerkos,2010). In this study, the effects of administration of two glucose analogs, the nonmetabolizable 3‐methylglucose (3MG) or the not fully metabolizable 2‐deoxyglucose (2DG), were studied.…”

“…During this period, hypoglycemia develops in the newborn following the abrupt stop in the mother‐to‐fetus glucose supply. This hypoglycemia results in the secretion of glucagon, which triggers few hours after birth, cellular responses such as glycogen autophagy to help the newborn cope with the need for glucose (Dawkins,1963; Girard et al,1973; Kalamidas and Kondomerkos,2010; Kotoulas and Phillips,1971; Kotoulas et al,1971,2004).…”

“…These phenomena mostly constitute an expression of glycogen autophagy, which is hormonally and metabolically regulated. Glucagon and adrenalin represent glycogen autophagy‐activating stimuli, whereas insulin and hyperglycemia represent suppressive stimuli (Kalamidas and Kondomerkos,2010; Kondomerkos et al,2005; Kotoulas and Phillips,1971; Kotoulas et al,2004; Rosenfeld,1964; Yin et al,2008). The intracellular signaling pathways of cAMP (inductive) and phosphoinositides/mTOR (inhibitory) converge on common targets such as the protein phosphatase PP2A to regulate glycogen autophagy (Kalamidas et al,2004; Kondomerkos et al,2005; Kotoulas,1986; Kotoulas et al,2006; Kundu and Thompson,2008).…”

Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

“…Most of the recent work on liver autophagy has focused on lipid digestion (lipophagy) (11,12) and glycogen digestion (13). There are few studies of liver lysosomal enzymes that act upon proteins and sulfated polysaccharides.…”