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Endocrinology. 2013 Oct;154(10):3502-14. doi: 10.1210/en.2012-2147. Epub 2013 Jul 26.

Conventional knockout of Tbc1d1 in mice impairs insulin- and AICAR-stimulated glucose uptake in skeletal muscle.

Author information

1
Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at the Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany. al-hasani@hhu.de.

Abstract

In the obesity-resistant SJL mouse strain, we previously identified a naturally occurring loss-of-function mutation in the gene for Tbc1d1. Characterization of recombinant inbred mice that carried the Tbc1d1(SJL) allele on a C57BL/6J background indicated that loss of TBC1D1 protects from obesity, presumably by increasing the use of fat as energy source. To provide direct functional evidence for an involvement of TBC1D1 in energy substrate metabolism, we generated and characterized conventional Tbc1d1 knockout mice. TBC1D1-deficient mice showed moderately reduced body weight, decreased respiratory quotient, and an elevated resting metabolic rate. Ex vivo analysis of intact isolated skeletal muscle revealed a severe impairment in insulin- and AICAR-stimulated glucose uptake in glycolytic extensor digitorum longus muscle and a substantially increased rate of fatty acid oxidation in oxidative soleus muscle. Our results provide direct evidence that TBC1D1 plays a major role in glucose and lipid utilization, and energy substrate preference in skeletal muscle.

PMID:
23892475
DOI:
10.1210/en.2012-2147
[Indexed for MEDLINE]

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