Hepatic glucose metabolism in late pregnancy normal versus high-fat and -fructose diet

Katie C. Coate, Marta S. Smith, Masakazu Shiota, Jose M. Irimia, Peter J. Roach, Ben Farmer, Phillip E. Williams, Mary Courtney Moore

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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 6 SEM NHGU was 105 6 9 mmol100 g liver21min21. The P and P-HFF dogs reached maximal NHGU in 90-120 min; their NHGU was blunted (68 6 9 and 16 6 17 mmol100 g liver21min21, 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.

Original languageEnglish (US)
Pages (from-to)753-761
Number of pages9
JournalDiabetes
Volume62
Issue number3
DOIs
StatePublished - Mar 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Coate, K. C., Smith, M. S., Shiota, M., Irimia, J. M., Roach, P. J., Farmer, B., Williams, P. E., & Moore, M. C. (2013). Hepatic glucose metabolism in late pregnancy normal versus high-fat and -fructose diet. Diabetes, 62(3), 753-761. https://doi.org/10.2337/db12-0875