Mechanism of Stimulation of Liver Glycogen Synthesis by Fructose in Alloxan Diabetic Rats

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, 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, glucose-6-phosphate increased by 84% (0.103 +/- 0.010 to 0.184 +/- 0.020 mumol/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 mumol/g wet wt at 10 min and remained below the control level.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of feeding, fasting, and diabetes on liver glycogen synthase activity, protein, and mRNA in rats

“…In diabetic animals, total synthase activity has been reported to be increased by a number of laboratories [2][3][4][5][6][7][8], including our own [1]. Bahnak and Gold reported the activity to be greater at 8 days of diabetes than at 3 days, but the differences were not as great as noted in the present study.…”

“…

Our laboratory [1], as well as many others [2][3][4][5][6][7][8] , have reported an increase in total synthase activity in liver from diabetic rats. The increase in hepatic synthase activity could be due to an increased mass of the enzyme or to the presence of a more catalytically efficient form(s) of the enzyme.

…”

The Impact of Fructose on Renal Function and Blood Pressure

“…Fructose is also known to stimulate glycogen accumulation in the liver [17, 18], which primarily appears to be due to inhibiting glycogenolysis due to inhibition of glycogen phosphorylase [19]. …”