MEASUREMENT OF HEPATIC R(A) UDP-GLUCOSE IN-VIVO IN RATS - RELATION TOGLYCOGEN 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 g alactose in hepatic UDP-Glc, sampled noninvasively by the xenobiotic g lucuronate (GlcUA) method, reveals R(a) UDP-Glc. First, labeling patte rns in secreted acetaminophen-GlcUA were compared with hepatic glycoge n and plasma glucose by use of mass isotopomer distribution analysis f rom [2-C-13]glycerol. Labeling was consistent with common precursor po ols of glucose 6-phosphate and triose-phosphate for all end products s tudied in fasted and in intravenous glucose- and fructose-infused stat es. Next, [1-H-3]galactose was administered. After a 24-h fast, R(a) U DP-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 infusio n rates of 111 and 167-194 mu mol . kg(-1) . min(-1), respectively. Li ver glycogen deposition correlated closely with R(a) UDP-Glc (R(2) = 0 .76), although the turnover value was similar to 50% higher than the n et deposition rate. In conclusion, the turnover of an intrahepatic met abolite, UDP-Glc, can be measured noninvasively, and R(a) UDP-Glc corr elates with liver glycogen deposition in rats.