title: Rate of glucose entry into hepatic uridine diphosphoglucose by the direct pathway in fasted and fed states in normal humans.
abstract: We used the glucuronate (GlcUA) probe technique to measure the rate of glucose entry into hepatic uridine diphosphoglucose (UDP-glc) by the direct pathway, to quantify the rate of appearance (Ra) of hepatic UDP-glc, and to calculate hepatic glucose cycling in vivo in normal humans. The direct pathway contribution to UDP-glc as determined by the ratio of [1-d1]-GlcUA to plasma [LD1]-glucose enrichments was minor (15% to 20%) in normal men after an overnight fast. After 9 hours of refeeding with intravenous (IV) glucose or an oral liquid formula meal each at a rate of 7 mg carbohydrate/kg/min, the direct pathway increased to 66.3% +/- 6.7% and 61.6% +/- 6.0% (mean +/- SE), respectively. Plasma glucose concentrations remained below 7.8 mmol/L and could not account for most of the variability in direct pathway contribution. The dilution of labeled [L-D1]-galactose in excreted acetaminophen-GlcUA was used to measure Ra UDP-glc, on the assumption that labeled galactose passes through the liver during its assimilation. Ra UDP-glc was 1.1 +/- 0.1 mg/kg/min after an overnight fast and increased to 2.0 +/- 0.1 with i.v. glucose and 2.6 +/- 0.2 with the oral liquid mixed meal. By combining the fractional glucose contribution with the Ra of hepatic UDP-glc, the rate of direct glucose entry into hepatic UDP-glc was 0.2 mg/kg/min (fasted) and increased to 1.3 to 1.6 (fed). This represented approximately 18% to 21% of systemic glucose disposal or 19% to 23% of the administered carbohydrate load during i.v. or oral refeeding.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California 94110.
authors.forename: M K
authors.initials: MK
authors.lastname: Hellerstein
authors.forename: S
authors.initials: S
authors.lastname: Kaempfer
authors.forename: J S
authors.initials: JS
authors.lastname: Reid
authors.forename: K
authors.initials: K
authors.lastname: Wu
authors.forename: C H
authors.initials: CH
authors.lastname: Shackleton
mesh_terms: D000082:Acetaminophen / Q000652:urine; D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D005215:Fasting; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014532:Uridine Diphosphate Glucose / Q000097:blood / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D000082:Acetaminophen; D005947:Glucose; D014532:Uridine Diphosphate Glucose