Evidence for suppression of hepatic glucose-6-phosphatase with carbohydrate feeding.
The mechanism by which exogenous glucose stimulates the incorporation of hepatic glucose-6-phosphate into glycogen in fasted rats has not been clearly delineated. We gave glucose intragastrically over a 3.5-h period during which liver glycogen was deposited at linear rates. Simultaneous primed continuous infusion of [2-3H] or [3-3H]glucose established that under these conditions absolute carbon flow through hepatic glucose-6-phosphatase was greatly suppressed. After 1 h, hepatic [UDP-glucose] and [glucose-6-phosphate] had fallen by 50-60% and the former remained low throughout the experiment. By contrast, [glucose-6-phosphate] rebounded to its initial value by 2 h and remained at this level during the subsequent hour. We interpret the data as follows. Exogenous glucose, in addition to acting as a precursor of liver glucose-6-phosphate, causes diversion of the latter away from free glucose formation and into glycogen synthesis. The fall in [UDP-glucose] is in accord with a glucose-induced activation of glycogen synthase, as proposed by Hers (Annu. Rev. Biochem. 1976; 45:167-89.). However, the fall-rise sequence of glucose-6-phosphate concentration constitutes the first direct evidence in vivo for simultaneous inhibition at the level of glucose-6-phosphatase.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008112:Liver Glycogen / Q000032:analysis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D008112:Liver Glycogen; D005952:Glucose-6-Phosphatase; D005947:Glucose