Measurement of hepatic Ra UDP-glucose in vivo in rats: relation to glycogen deposition and labeling patterns.
We previously described an isotopic method for quantifying the rate of appearance of hepatic UDP-glucose (Ra UDP-Glc) and the direct entry of glucose into hepatic UDP-Glc in humans. Here, the method is tested in depth in rats. The basic principles are that dilution of labeled galactose in hepatic UDP-Glc, sampled noninvasively by the xenobiotic glucuronate (GlcUA) method, reveals Ra UDP-Glc. First, labeling patterns in secreted acetaminophen-GlcUA were compared with hepatic glycogen and plasma glucose by use of mass isotopomer distribution analysis from [2-(13)C]glycerol. Labeling was consistent with common precursor pools of glucose 6-phosphate and triose-phosphate for all end products studied in fasted and in intravenous glucose- and fructose-infused states. Next, [1-(3)H]galactose was administered. After a 24-h fast, Ra UDP-Glc was 25.0 +/- 1.7 mumol.kg body wt-1.min-1 and rose to 57.7 and 72.7 mumol.kg-1.min-1 at intravenous glucose infusion rates of 111 and 167-194 mumol.kg-1.min-1, respectively. Liver glycogen deposition correlated closely with Ra UDP-Glc (R2 = 0.76), although the turnover value was approximately 50% higher than the net deposition rate. In conclusion, the turnover of an intrahepatic metabolite, UDP-Glc, can be measured noninvasively, and Ra UDP-Glc correlates with liver glycogen deposition in rats.
Hellerstein
M K
MK
Department of Nutritional Sciences, University of California, Berkeley 94720-3104, USA.
Letscher
A
A
Schwarz
J M
JM
César
D
D
Shackleton
C H
CH
Turner
S
S
Neese
R
R
Wu
K
K
Bock
S
S
Kaempfer
S
S
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002247:Carbon Isotopes; D005215:Fasting; D005947:Glucose / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D008297:Male; D008722:Methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D014532:Uridine Diphosphate Glucose / Q000378:metabolism*
D001786:Blood Glucose; D002247:Carbon Isotopes; D006003:Glycogen; D005947:Glucose; D005990:Glycerol; D014532:Uridine Diphosphate Glucose