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Net hepatic glucose uptake (NHGU) is an important contributor to postprandial glycemic control. We hypothesized that NHGU is reduced during normal pregnancy and in a pregnant diet-induced model of impaired glucose intolerance/gestational diabetes mellitus (IGT/GDM). Dogs (n = 7 per group) that were nonpregnant (N), normal pregnant (P), or pregnant with IGT/GDM (pregnant dogs fed a high-fat and -fructose diet [P-HFF]) underwent a hyperinsulinemic-hyperglycemic clamp with intraportal glucose infusion. Clamp period insulin, glucagon, and glucose concentrations and hepatic glucose loads did not differ among groups. The N dogs reached near-maximal NHGU rates within 30 min; mean ± SEM NHGU was 105 ± 9 µmol 100 g liver^sup -1^ min^sup -1^. The P and P-HFF dogs reached maximal NHGU in 90-120 min; their NHGU was blunted (68 ± 9 and 16 ± 17 µmol.100 g liver^sup -1^.min^sup -1^, respectively). Hepatic glycogen synthesis was reduced 20% in P versus N and 40% in P-HFF versus P dogs. This was associated with a reduction (>70%) in glycogen synthase activity in P-HFF versus P and increased glycogen Phosphorylase (GP) activity in both P (1.7-fold greater than N) and P-HFF (1.8-fold greater than P) dogs. Thus, NHGU under conditions mimicking the postprandial state is delayed and suppressed in normal pregnancy, with concomitant reduction in glycogen storage. NHGU is further blunted in IGT/GDM. This likely contributes to postprandial hyperglycemia during pregnancy, with potential adverse outcomes for the fetus and mother. Diabetes 62:753-761, 2013
Net hepatic glucose balance is the sum of two processes, hepatic glucose output (HGO) and hepatic glucose uptake (HGU), which often occur simultaneously. Net hepatic glucose uptake (NHGU) is observed after ingestion of a glucose load or mixed meal in healthy individuals as a result of suppression of HGO and stimulation of HGU. In normalweight pregnant women without diabetes but not obese women without diabetes and women with gestational diabetes mellitus (GDM), HGO under hyperinsulinemiceuglycemic clamp conditions remains sensitive to suppression by hyperinsulinemia (1-3). However, the effect of pregnancy (either in normal-weight or obese women or in women with diabetes) on HGU under postprandial conditions remains virtually unexplored. After a mixed meal, NHGU is indistinguishable between pregnant and nonpregnant rabbits (4) and higher in pregnant than in nonpregnant dogs (5). However, glucose and insulin concentrations differ between...