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Am J Physiol Endocrinol Metab (March 29, 2005). doi:10.1152/ajpendo.00601.2004
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Submitted on December 20, 2004
Accepted on February 14, 2005

Effect of Murine Strain on Metabolic Pathways of Glucose Production after Brief or Prolonged Fasting

Shawn C Burgess1*, F Mark Jeffrey1, Charles Storey1, Angela Milde1, Natasha Hausler1, Matthew E Merritt1, Hindrik Mulder1, Cecilia Holm1, A Dean Sherry1, and Craig R Malloy1

1 Radiology, University of Texas Southwestern Medical Center, Dallas, Tx, USA

* To whom correspondence should be addressed. E-mail: shawn.burgess{at}utsouthwestern.edu.

Background strain is known to influence on 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 129S1/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-hour fast, B6 mice retain some residual glycogenolysis compared to other strains. FVB mice also had a 30% higher in vivo PEPCK flux and total glucose production from the level of the TCA cycle compared to B6 and 129 strains while total body glucose production in the 129 strain was ~30% lower than 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.




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