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Noninvasive Analysis of Hepatic Glycogen Kinetics Before and After Breakfast with Deuterated Water and Acetaminophen

¹ NMR Research Unit, Department of Biochemistry and Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal
² Department of Endocrinology, University Hospital of Coimbra, Coimbra, Portugal
³ Department of Chemistry, University of Coimbra, Coimbra, Portugal

Address correspondence and reprint requests to John G. Jones, DSc, NMR Research Unit, Department of Biochemistry and Center for Neurosciences and Cell Biology, Faculty of Sciences and Technology, University of Coimbra, 3001-401 Coimbra, Portugal. E-mail: jones{at}cnc.cj.uc.pt

Abbreviations: DMF, dimethylformamide; F6P, fructose-6-phosphate; G1P, glucose-1-phosphate; G6P, glucose-6-phosphate; MAG, monoacetone glucose; NMR, nuclear magnetic resonance; UDPG, uridine diphosphate glucose

The contributions of hepatic glycogenolysis to fasting glucose production and direct pathway to hepatic glycogen synthesis were quantified in eight type 1 diabetic patients and nine healthy control subjects by ingestion of ²H₂O and acetaminophen before breakfast followed by analysis of urinary water and acetaminophen glucuronide. After overnight fasting, enrichment of glucuronide position 5 relative to body water (G5/body water) was significantly higher in type 1 diabetic patients compared with control subjects, indicating a reduced contribution of glycogenolysis to glucose production (38 ± 3 vs. 46 ± 2%). Following breakfast, G5/body water was significantly higher in type 1 diabetic patients, indicating a smaller direct pathway contribution to glycogen synthesis (47 ± 2 vs. 59 ± 2%). Glucuronide hydrogen 2 enrichment (G2) was equivalent to body water during fasting (G2/body water 0.94 ± 0.03 and 1.02 ± 0.06 for control and type 1 diabetic subjects, respectively) but was significantly lower after breakfast (G2/body water 0.78 ± 0.03 and 0.82 ± 0.05 for control and type 1 diabetic subjects, respectively). The reduced postprandial G2 levels reflect incomplete glucose-6-phosphate–fructose-6-phosphate exchange or glycogen synthesis from dietary galactose. Unlike current measurements of human hepatic glycogen metabolism, the ²H₂O/acetaminophen assay does not require specialized on-site clinical equipment or personnel.

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