Journal
DIABETES
Volume 50, Issue 6, Pages 1263-1268Publisher
AMER DIABETES ASSOC
DOI: 10.2337/diabetes.50.6.1263
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Funding
- NCRR NIH HHS [MO1 RR-00125] Funding Source: Medline
- NIDDK NIH HHS [P30 DK-45735, R01 DK-42930] Funding Source: Medline
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Fructose has been shown to have a catalytic effect on glucokinase activity in vitro; however, its effects on hepatic glycogen metabolism in humans is unknown. To address this question, we used C-13 nuclear magnetic resonance (NMR) spectroscopy to noninvasively assess rates of hepatic glycogen synthesis and glycogenolysis under euglycemic (similar to5 mmol/l) hyperinsulinemic conditions (similar to 400 pmol/l) with and without a low-dose infusion of fructose (similar to3,5 mu mol.kg(-1).min(-1)). Six healthy overnight-fasted subjects were infused for 4 h with somatostatin (0.1 mug.kg(-1).min(-1)) and insulin (240 pmol.m(-2).min(-1)). During the initial 120 min, [1(-13)C]glucose was infused to assess glycogen synthase flux followed by an similar to 120-min infusion of unlabeled glucose to assess rates of glycogen phosphorylase flux. Acetaminophen was given to assess the percent contribution of the direct and indirect (gluconeogenic) pathways of glycogen synthesis by the C-13 enrichment of plasma UDP-glucuronide and C-1 of glucose. In the control studies, the flux through glycogen synthase and glycogen phosphorylase was 0.31 +/- 0.06 and 0.17 +/- 0.04 mmol/l per min, respectively, and the rate of net hepatic glycogen synthesis was 0.14 +/- 0.05 mmol/l per min, In the fructose studies, the glycogen synthase flux increased 2.5-fold to 0.79 +/- 0.16 mmol/l per min (P = 0.018 vs. control), whereas glycogen phosphorylase flux remained unchanged (0.24 +/- 0.06; P = 0.16 vs. control). The infusion of fructose resulted in a threefold increase in rates of net hepatic glycogen synthesis (0.54 +/- 0.12 mmol/l per min; P = 0.008 vs. control) without affecting the pathways of hepatic glycogen synthesis (direct pathway similar to 60% in both groups). We conclude that during euglycemic hyperinsulinemia, a low-dose fructose infusion causes a threefold increase in net hepatic glycogen synthesis exclusively through stimulation of glycogen synthase flux. Because net hepatic glycogen synthesis has been shown to be diminished in patients with poorly controlled type 1 and type 2 diabetes, stimulation of hepatic glycogen synthesis by this mechanism may be of potential therapeutic value.
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