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AJP - Endocrinology and Metabolism, Vol 272, Issue 1 E155-E162, Copyright © 1997 by American Physiological Society
ARTICLES |
M. K. Hellerstein, A. Letscher, J. M. Schwarz, D. Cesar, C. H. Shackleton, S. Turner, R. Neese, K. Wu, S. Bock and S. Kaempfer
Department of Nutritional Sciences, University of California, Berkeley 94720-3104, USA.
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.
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