Effect of murine strain on metabolic pathways of glucose production after brief or prolonged fasting

Shawn C. Burgess, F. Mark H Jeffrey, Charles Storey, Angela Milde, Natasha Hausler, Matthew E. Merritt, Hindrik Mulder, Cecilia Holm, A. Dean Sherry, Craig R. Malloy

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Background strain is known to influence the way a genetic manipulation affects mouse phenotypes. Despite data that demonstrate variations in the primary phenotype of basic inbred strains of mice, there is limited data available about specific metabolic fluxes in vivo that may be responsible for the differences in strain phenotypes. In this study, a simple stable isotope tracer/NMR spectroscopic protocol has been used to compare metabolic fluxes in ICR, FVB/N (FVB), C57BL/6J (B6), and 12981/SvImJ (129) mouse strains. After a short-term fast in these mice, there were no detectable differences in the pathway fluxes that contribute to glucose synthesis. However, after a 24-h fast, B6 mice retain some residual glycogenolysis compared with other strains. FVB mice also had a 30% higher in vivo phosphoeno/pyruvate carboxykinase flux and total glucose production from the level of the TCA cycle compared with B6 and 129 strains, while total body glucose production in the 129 strain was ∼30% lower than in either FVB or B6 mice. These data indicate that there are inherent differences in several pathways involving glucose metabolism of inbred strains of mice that may contribute to a phenotype after genetic manipulation in these animals. The techniques used here are amenable to use as a secondary or tertiary tool for studying mouse models with disruptions of intermediary metabolism.

Original languageEnglish (US)
Pages (from-to)E53-E61
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume289
Issue number1 52-1
DOIs
StatePublished - Jul 2005

Keywords

  • Deuterium
  • Metabolic flux
  • Mouse phenotype
  • Nuclear magnetic resonance
  • Phosphoenolpyruvate carboxykinase
  • Stable isotope tracers
  • Tricarboxylic acid cycle

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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