Mechanism of stimulation of liver glycogen synthesis by fructose in alloxan diabetic rats

C. B. Niewoehner, F. Q. Nuttall

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Abstract

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, active 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 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, glucose-6-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. ATP, P(i), 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.

Original languageEnglish (US)
Pages (from-to)705-711
Number of pages7
JournalDiabetes
Volume35
Issue number6
DOIs
StatePublished - Jan 1 1986

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