Mechanism of stimulation of liver glycogen synthesis by fructose in alloxan diabetic rats.
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)
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005632:Fructose / Q000378:metabolism / Q000494:pharmacology*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006006:Glycogen Synthase / Q000032:analysis; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects*; D008112:Liver Glycogen / Q000096:biosynthesis*; D008297:Male; D010762:Phosphorylase a / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014532:Uridine Diphosphate Glucose / Q000378:metabolism
D005958:Glucosephosphates; D007773:Lactates; D008112:Liver Glycogen; D005632:Fructose; D019344:Lactic Acid; D019298:Glucose-6-Phosphate; D010762:Phosphorylase a; D006006:Glycogen Synthase; D014532:Uridine Diphosphate Glucose