Immediately after the last meal on day 20 of gestation. (term=21), the rat was anaesthetized with sodium pentobarbital. The liver was exposed and the hepatic ...
Biochemical SocietyTransactions ( 1 993) 21
453s
In vivo hepatic glucose disposal during pregnancy. K. Kumar Changani, 'Steve C.R. Williams and Richard A. Iles. Medical Unit, Cellular Mechanisms Research Group, The London Hospital Medical College, London E l lBB, UK. 'NMR Unit, Queen Mary & Westfield College, London E l 4NS. Pregnancy places many demands on the mother both physiologically and metabolically. The mother must sustain nument balance to both herself and the developing fetus(es). As a consequence, late pregnancy is associated with insulin resistance [ 13 and glucose intolerance together with increased lipid and ketone body circulation and utilization by a wide range of tissue types [2]. It is thought that these and other metabolic changes ensure channeling of the blood glucose to the uterine system, suggesting that glucose is a preferred fuel substrate for the conceptus, possibly due to the ease of mobilization and transport of glucose, or glucose oxidation processes being the better developed. The liver controls glucose homeostasis, therefore for increased knowledge of the pathogenesis of insulin resistant states, studies of the kinetics of hepatic glucose disposal are necessary. In this study proton-decoupled carbon- 13 magnetic resonance spectroscopy (MRS) has been employed as a tool for in vivo hepatic measurements to elucidate the liver's glucose utilizatioddisposal capacity during pregnancy. Two groups of age-matched female albino Wistar rats were time-mated. One group was allowed food ad libitum [Group I] whereas Group I1 (routinely meal fed-RMF [3]) were transferred to a reverse lighvdark mom [light off 10:00/light on 22:00] and allowed access to chow for 2hr/day from day 5 of pregnancy. Group ID were age-matched virgin controls fed ad libitum. Immediately after the last meal on day 20 of gestation (term=21), the rat was anaesthetized with sodium pentobarbital. The liver was exposed and the hepatic portal vein cannulated to a line containing D-glucose-l-'3C(99atom % I3C) [2OOmg/ml]. A dual-tuned protodcarbon coil was placed directly on top of the liver and the animal placed into the bore of the magnet. Using a 4.7 Tesla, 33cm horizontal bore imaging spectrometer, proton-decoupled carbon spectra were acquired at 50.309MHz with an acquisition time of 0.205s, relaxation time of O.ls, a pulse width of 70ps and spectral width of 12kHz. Spectra were accumulated every 2.5min over a 65min period. After accumulation of two base-line spectra, D-glucose-1'3C[75mg;30mg.min-'] was infused. Spectra were referenced to C-1, I3 glucose at 96.60ppm. The C-1 glycogen resonance at 100.48ppm was evaluated. Glucose disposal and glycogen synthesis rates were assessed from the relative peak areas normalized to the -CH, integrated area which, from lipid extraction studies, remains constant in the fed groups. From Fig. I , very little incorporation of "C-glucose into glycogen was detected in Groups I and 111, whereas Group I1 had a much enhanced incorporation rate, in an approximately linear fashion. Glucose profiles of the three groups indicate relatively slow removal of glucose from the splanchnic region in Groups 11 and 111 in contrast to Group I. Late pregnancy is shown to diminish intracellular glucose utilization by the liver, reflected in the lack of glucose assimilation and utilization compared with the same fed virgin condition whereas by routine meal feeding, enhanced glucose uptake and incorporation into glycogen can be seen in gestationally the same condition. This study suggests an important change in glucose homeostasis by the liver during pregnancy and the importance of MRS for investigating in vivo glucose kinetics.
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Figure I - a ad libitum, 20 day pregnant (group I);( 1 RMF, 20 day pregnant (group 11); T ad libitum, virgin (group I l l ) . Glycogen integral values represent net synthesis afrer "Cglucose infusion. All integral values are normalized to the CH, integrated area.
1. Ogata, E.S., Metzger, B.E. & Freinkel, N. (1981) Metab. Clin. Exp. 30, 4877-492. 2. Holness, M.J., Changani, K.K. & Sugden, M.C. (1991) Biochem. J. 280 549-552. 3. Pallardo, F.V. & Williamson, D.H. (1989) Biochem. J . 257 607-610. We thank the Peel Medical Research Trust and the University of London Central Research Fund for their support and the University of London Intercollegiate Research Service (ULIRS) for access to the NMR imaging spectrometer at QMW.
