In diabetic animals and humans, stimulation of liver glycogen synthesis has been reported after administration of a large parenteral fructose load. The effects of an oral fructose load have not been examined previously. In the diabetic state, glycogen synthase phosphatase activity is reduced, and synthase D (the inactive form) is a poor substrate for the phosphatase. Thus,activation of synthase to the synthase R and synthase I (R + I) (active) forms by fructose would not be expected. We have determined that oral fructose administration does stimulate glycogen synthesis and have examined the mechanism by which this is accomplished. In 24-h-fasted alloxan diabetic rats, basal liver glycogen was higher than in normal rats (8.3 ±1.8 vs. 3.0 ± 0.5 mg/g wet wt). After fructose (4 g/kg) was given, the initial rate of glycogen synthesis was normal in diabetic rats, but total glycogen synthesis was reduced. By 240 min, liver glycogen increased to 18 ± 4.0 mg/g wet wt in diabetic rats versus 30.5 ±1.5 mg/g wet wt in normal rats. Synthase R + I was low and did not increase significantly (0.063 ± 0.006 to 0.064 ± 0.010 U/g wet wt) after fructose administration to the diabetic animals. Phosphorylase a did not decrease significantly during the period of active glycogen synthesis. In the diabetic rats, glucoses-phosphate increased by 84% (0.103 ± 0.010 to 0.184 ± 0.020 μmol/g wet wt) within 10 min and remained elevated above the control level. UDPglucose decreased from 0.336 ± 0.013 to 0.271 ± 0.011 μmol/g wet wt at 10 min and remained below the control level. ATP1, P1 and cAMP were unchanged.These data are compatible with a “pull” mechanism of glycogen synthesis due to stimulation of synthase R activity by a rise in glucose-6-P, with little conversion of synthase to the more active R + I forms. They do not suggest a substrate push mechanism for stimulation of glycogen synthesis by fructose in diabetic rats.
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Original Contribution| June 01 1986
Mechanism of Stimulation of Liver Glycogen Synthesis by Fructose in Alloxan Diabetic Rats
Catherine B Niewoehner;
Address reprint requests to Catherine B. Niewoehner, M.D., Endocrine Metabolic Section, Veterans Administration Medical Center, 54th Street and 48th Avenue South, Minneapolis, MN 55417.
Catherine B Niewoehner, Frank Q Nuttall; Mechanism of Stimulation of Liver Glycogen Synthesis by Fructose in Alloxan Diabetic Rats. Diabetes 1 June 1986; 35 (6): 705–711. https://doi.org/10.2337/diab.35.6.705
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