The administration of nonmetabolizable glucose analogues fails to suppress the development of glycogen autophagy in newborn rat hepatocytes.
The effects of parenteral administration of glucose, 3-methylglucose (3MG), or 2-deoxyglucose (2DG) on the glycogen autophagy were studied in the newborn rat liver using electron microscopy and biochemical methods. The administration of glucose resulted in hyperglycemia and prevented the mobilization of hepatocytic glycogen. It also prevented the development of autophagic vacuoles in general and inhibited the glycogen-degrading activity of acid α-1,4-glucosidase. The nonphosphorylated and not further metabolized glucose analog 3MG also produced hyperglycemia, but increased acid glucosidase. Pretreating the newborns with the β-adrenergic blocker propranolol inhibited the effects of 3MG. The phosphorylated but not fully metabolized glucose analog 2DG produced similar effects. The administration of xylitol to the newborns already treated with 2DG, suppressed acid glucosidase. The results of this and our previous studies suggest that glucose must be metabolized beyond its phosphorylation step to inhibit acid glucosidase activity.
Kalamidas
Stefanos A
SA
Department of Anatomy, Histology and Embryology, Medical School, University of Ioannina, Ioannina 45110, Greece. skalamid@cc.uoi.gr
Kondomerkos
Dimitrios J
DJ
D019325:3-O-Methylglucose / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001343:Autophagy / Q000187:drug effects*; D001786:Blood Glucose; D003847:Deoxyglucose / Q000008:administration & dosage / Q000494:pharmacology; D005087:Glucan 1,4-alpha-Glucosidase / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006003:Glycogen / Q000737:chemistry / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006651:Histocytochemistry; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D008853:Microscopy; D010784:Photomicrography; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014617:Vacuoles / Q000737:chemistry / Q000378:metabolism
D001786:Blood Glucose; D019325:3-O-Methylglucose; D006003:Glycogen; D003847:Deoxyglucose; D011433:Propranolol; D005087:Glucan 1,4-alpha-Glucosidase; D005947:Glucose