Hepatic Glucose Metabolism in Late Pregnancy
Normal Versus High-Fat and -Fructose Diet
- Katie C. Coate1,
- Marta S. Smith1,
- Masakazu Shiota1,
- Jose M. Irimia2,
- Peter J. Roach2,
- Ben Farmer1,
- Phillip E. Williams3,4 and
- Mary Courtney Moore1⇓
- 1Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee
- 2Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana
- 3Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee
- 4Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee
- Corresponding author: Mary Courtney Moore, .
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−1⋅min−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−1⋅min−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.
- Received June 29, 2012.
- Accepted September 11, 2012.
- © 2013 by the American Diabetes Association.
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