Effects of graded intravenous doses of fructose on glycogen synthase in the liver of fasted rats

• Published in: Metabolism, clinical and experimental Vol. 36; no. 4; p. 338
• Main Authors: Niewoehner, C B, Nuttall, B Q, Nuttall, F Q
• Format: Journal Article
• Language: English
• Published: United States 01.04.1987
• Subjects: Animals; Fasting; Fructose - administration & dosage; Glucose-6-Phosphate; Glucosephosphates - metabolism; Glycogen Synthase - metabolism; Injections, Intravenous; Liver - enzymology; Liver - metabolism; Male; Phosphorylase a - metabolism; Rats; Rats, Inbred Strains
• ISSN: 0026-0495
• DOI: 10.1016/0026-0495(87)90204-6

We have examined in fasted rats the effects of graded doses of intravenous fructose (50 to 500 mg/kg) in order to determine potential mechanisms by which different concentrations of fructose reaching the liver may modify the activity of glycogen synthase (and phosphorylase). With increasing fructose doses the % synthase I increased threefold to a maximum at a dose of 125 mg/kg and then decreased progressively after higher fructose doses were given. The % phosphorylase a decreased by 30% to a minimum at a dose of 125 mg/kg but increased with higher doses to 370% of the control values. Both the % synthase I and the % phosphorylase a were elevated above the control values at fructose doses of 175 to 225 mg/kg. The increase in % synthase I after low doses of fructose occurred with a significant increase in glucose-6-P but no significant change in hepatic fructose, glucose, UDPglucose, ATP/Mg++, Pi, cAMP, plasma insulin, or glucagon concentrations. The reciprocal decrease in % synthase I and increase in % phosphorylase a occurred despite increases in glucose and glucose-6-P, at fructose doses resulting in no change in ATP/Mg++, Pi or cAMP, and only a small increase (0.39 mmol/L) in the fructose-1-P concentration. We propose that activation of synthase phosphatase by a rise in the glucose-6-P concentration is responsible for the increase in % synthase I after low doses of fructose. The mechanism by which higher fructose doses overcome the expected activation of synthase phosphatase by glucose and glucose-6-P and a decreased ATP/Mg++ ratio is uncertain.