Measurement of hepatic R(a) 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 (R(a) 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 R(a) 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-C-13]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-H-3]galactose was administered. After a 24-h fast, R(a) UDP-Glc was 25.0 +/- 1.7 mu mol . kg body wt(-1) . min(-1) and rose to 57.7 and 72.7 mu mol . kg(-1) . min(-1) at intravenous glucose infusion rates of 111 and 167-194 mu mol . kg(-1) . min(-1), respectively. Liver glycogen deposition correlated closely with R(a) UDP-Glc (R(2) = 0.76), although the turnover value was similar to 50% higher than the net deposition rate. In conclusion, the turnover of an intrahepatic metabolite, UDP-Glc, can be measured noninvasively, and R(a) UDP-Glc correlates with liver glycogen deposition in rats.