INCORPORATION OF [3-H-3]GLUCOSE AND 2-[1-C-14]DEOXYGLUCOSE INTO GLYCOGEN IN HEART AND SKELETAL-MUSCLE IN-VIVO - IMPLICATIONS FOR THE QUANTITATION OF TISSUE GLUCOSE-UPTAKE

2-deoxyglucose has been widely used to quantitate tissue glucose uptak e in vivo, assuming that a-deoxyglucose is transported and phosphoryla ted but not further metabolized. We examined the validity of this assu mption by infusing [3-H-3]glucose and 2-[1-C-14]deoxyglucose in a simi lar primed continuous fashion to chronically catheterized, freely movi ng rats during normoglycemic hyperinsulinemic conditions. The rates of 2-deoxyglucose uptake were determined from the accumulation of 2-[1-C -14]deoxyglucose-6-phosphate and 2-[1-C-14]deoxyglucose-6-phosphate co mbined with the rate of the incorporation of 2-[1-C-14]deoxyglucose in to glycogen in rectus abdominis muscle and the heart. When the rates o f glycogen synthesis during the 2-h hyperinsulinemic period from the t wo tracers were compared in rectus abdominis muscle, the rate of glyco gen synthesis was twofold higher when measured with [3-H-3]glucose (33 7 +/- 14 mu mol.kg(-1).min(-1)) than when measured with 2-[1-C-14]deox yglucose (166 +/- 10 mu mol kg(-1).min(-1), P < 0.001). In the heart, the rate of glycogen synthesis was twofold higher when measured with 2 -[1-C-14]deoxyglucose (141 +/- 20 mu mol.kg(-1).min(-1)) than when mea sured with [3-H-3]glucose (72 +/- 15 mu mol.kg(-1).min(-1), P < 0.001) . The rate of 2-deoxyglucose uptake was 29% underestimated in rectus a bdominis muscle, when counts found in glycogen were not included in gl ucose uptake calculations (398 +/- 25 vs. 564 +/- 25 mu mol.kg(-1).min (-1), P < 0.001). In the heart, glucose uptake was underestimated by 7 % if glycogen counts were not taken into account (1,786 +/- 278 vs. 1, 926 +/- 291 mu mol.kg(-1) dry.min(-1), P < 0.05). The fraction of [3-H -3]glucose incorporated into glycogen of total glucose metabolism (cal culated from 2-deoxyglucose conversion to 2-deoxyglucose-6-phosphate a nd glycogen) was 0.6 (337/564) in rectus abdominis muscle and 0.037 (7 2/1,926) in the heart. We conclude that 2-deoxyglucose is incorporated into glycogen in the heart and in skeletal muscle in vivo under normo glycemic hyperinsulinemic conditions in the rat. Failure to consider t he incorporation of 2-deoxyglucose into glycogen will underestimate th e rate of tissue glucose uptake. To avoid such problems, the amount of 2-deoxyglucose incorporated into glycogen should be quantitated in su bsequent studies.