An endogenous glycogen-associated compound modulates glucose-6-phosphatase activity in rat liver microsomes.
Liver glycogen is closely associated with the endoplasmic reticulum, which contains the glucose-6-phosphatase enzyme system that catalyses the final step of hepatic glucose production. To examine whether this structural association has functional consequences, microsomes were isolated from 48 h fasted (n = 6) and ad lib fed rats (n = 3). Microsomes from fed rats had a higher glycogen content and lower enzyme activity than fasted rats. Overall, glucose-6-phosphatase activity was inversely proportional to microsomal glycogen content. Partially purified rabbit or rat liver glycogen, at physiological relevant concentrations (10-100 mM glucose equivalents), added directly to either intact or Triton-disrupted microsomes from fasted rats significantly decreased glucose-6-phosphatase activity. Inhibitory activity was present in native liver glycogen prepared by sedimentation and could be dissociated from glycogen by ion-exchange and ultrafiltration. These findings suggest that a low molecular weight (< 5000 D) compound closely associated with glycogen can modulate glucose-6-phosphatase and may have a physiologic role in the regulation of hepatic glucose production.
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
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Z
Liu
L B
LB
Gardner
E J
EJ
Barrett
D000818:Animals; D004435:Eating; D005215:Fasting; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008112:Liver Glycogen / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D008112:Liver Glycogen; D005952:Glucose-6-Phosphatase