In:
Diabetes, American Diabetes Association, Vol. 50, No. 6 ( 2001-06-01), p. 1263-1268
Abstract:
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 13C nuclear magnetic resonance (NMR) spectroscopy to noninvasively assess rates of hepatic glycogen synthesis and glycogenolysis under euglycemic (∼5 mmol/l) hyperinsulinemic conditions (∼400 pmol/l) with and without a low-dose infusion of fructose (∼3.5 μmol · kg–1 · min–1). Six healthy overnight-fasted subjects were infused for 4 h with somatostatin (0.1 μg · kg–1 · min–1) and insulin (240 pmol · m–2 · min–1). During the initial 120 min, [1-13C]glucose was infused to assess glycogen synthase flux followed by an ∼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 13C 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 ∼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.
Type of Medium:
Online Resource
ISSN:
0012-1797
,
1939-327X
DOI:
10.2337/diabetes.50.6.1263
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2001
detail.hit.zdb_id:
1501252-9
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