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

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 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-h fast, B6 mice retain some residual glycogenolysis compared with other strains. FVB mice also had a 30% higher in vivo phosphoenolpyruvate 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 similar to 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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
stable isotope
metabolic flux
phosphoenolpyruvate carboxykinase
nuclear magnetic resonance
tricarboxylic acid cycle
tracers
deuterium
mouse phenotype

Jeffrey, FMH (author)
Storey, C (author)
Milde, A (author)
Hausler, N (author)
Merritt, ME (author)
Mulder, HindrikLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)medk-hmu (author)
Holm, CeciliaLund University,Lunds universitet,Molekylär endokrinologi,Forskargrupper vid Lunds universitet,Molecular Endocrinology,Lund University Research Groups(Swepub:lu)medk-cho (author)
Sherry, AD (author)
Malloy, CR (author)
Diabetes - molekylär metabolismForskargrupper vid Lunds universitet (creator_code:org_t)

In:American Journal of Physiology: Endocrinology and Metabolism: American Physiological Society289:1, s. 53-611522-15550193-1849

By the author/editor: Burgess, SC; Jeffrey, FMH; Storey, C; Milde, A; Hausler, N; Merritt, ME; show more...; Mulder, Hindrik; Holm, Cecilia; Sherry, AD; Malloy, CR; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

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