RGD Reference Report - Ablating the protein TBC1D1 impairs contraction-induced sarcolemmal glucose transporter 4 redistribution but not insulin-mediated responses in rats. - Rat Genome Database

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Ablating the protein TBC1D1 impairs contraction-induced sarcolemmal glucose transporter 4 redistribution but not insulin-mediated responses in rats.

Authors: Whitfield, Jamie  Paglialunga, Sabina  Smith, Brennan K  Miotto, Paula M  Simnett, Genevieve  Robson, Holly L  Jain, Swati S  Herbst, Eric A F  Desjardins, Eric M  Dyck, David J  Spriet, Lawrence L  Steinberg, Gregory R  Holloway, Graham P 
Citation: Whitfield J, etal., J Biol Chem. 2017 Oct 6;292(40):16653-16664. doi: 10.1074/jbc.M117.806786. Epub 2017 Aug 14.
RGD ID: 150521563
Pubmed: PMID:28808062   (View Abstract at PubMed)
PMCID: PMC5633127   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M117.806786   (Journal Full-text)

TBC1 domain family member 1 (TBC1D1), a Rab GTPase-activating protein and paralogue of Akt substrate of 160 kDa (AS160), has been implicated in both insulin- and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase-mediated glucose transporter type 4 (GLUT4) translocation. However, the role of TBC1D1 in contracting muscle remains ambiguous. We therefore explored the metabolic consequence of ablating TBC1D1 in both resting and contracting skeletal muscles, utilizing a rat TBC1D1 KO model. Although insulin administration rapidly increased (p < 0.05) plasma membrane GLUT4 content in both red and white gastrocnemius muscles, the TBC1D1 ablation did not alter this response nor did it affect whole-body insulin tolerance, suggesting that TBC1D1 is not required for insulin-induced GLUT4 trafficking events. Consistent with findings in other models of altered TBC1D1 protein levels, whole-animal and ex vivo skeletal muscle fat oxidation was increased in the TBC1D1 KO rats. Although there was no change in mitochondrial content in the KO rats, maximal ADP-stimulated respiration was higher in permeabilized muscle fibers, which may contribute to the increased reliance on fatty acids in resting KO animals. Despite this increase in mitochondrial oxidative capacity, run time to exhaustion at various intensities was impaired in the KO rats. Moreover, contraction-induced increases in sarcolemmal GLUT4 content and glucose uptake were lower in the white gastrocnemius of the KO animals. Altogether, our results highlight a critical role for TBC1D1 in exercise tolerance and contraction-mediated translocation of GLUT4 to the plasma membrane in skeletal muscle.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SD-Tbc1d1Tn(sb)1FkhRatabnormal carbohydrate metabolism inducesIMPcontrolled visible light condition RGD 
Tbc1d1Ratabnormal carbohydrate metabolism inducesIMPcontrolled visible light condition RGD 
Tbc1d1Tn(sb)1FkhRatabnormal carbohydrate metabolism inducesIMPcontrolled visible light condition RGD 
SD-Tbc1d1Tn(sb)1FkhRatabnormal respiratory function inducesIMPnucleoside/nucleotide RGD 
Tbc1d1Ratabnormal respiratory function inducesIMPnucleoside/nucleotide RGD 
Tbc1d1Tn(sb)1FkhRatabnormal respiratory function inducesIMPnucleoside/nucleotide RGD 
SD-Tbc1d1Tn(sb)1FkhRatdecreased muscle cell glucose uptake inducesIMPdirect electrical nerve stimulationcompared to Wild typeRGD 
Tbc1d1Ratdecreased muscle cell glucose uptake inducesIMPdirect electrical nerve stimulationcompared to Wild typeRGD 
Tbc1d1Tn(sb)1FkhRatdecreased muscle cell glucose uptake inducesIMPdirect electrical nerve stimulationcompared to Wild typeRGD 
SD-Tbc1d1Tn(sb)1FkhRatincreased circulating glucose level inducesIMPglucosecompared to Wild typeRGD 
Tbc1d1Ratincreased circulating glucose level inducesIMPglucosecompared to Wild typeRGD 
Tbc1d1Tn(sb)1FkhRatincreased circulating glucose level inducesIMPglucosecompared to Wild typeRGD 
SD-Tbc1d1Tn(sb)1FkhRatincreased creatine level inducesIMPdirect electrical nerve stimulation RGD 
Tbc1d1Ratincreased creatine level inducesIMPdirect electrical nerve stimulation RGD 
Tbc1d1Tn(sb)1FkhRatincreased creatine level inducesIMPdirect electrical nerve stimulation RGD 
SD-Tbc1d1Tn(sb)1FkhRatincreased fatty acid oxidation inducesIMPcontrolled visible light condition RGD 
Tbc1d1Ratincreased fatty acid oxidation inducesIMPcontrolled visible light condition RGD 
Tbc1d1Tn(sb)1FkhRatincreased fatty acid oxidation inducesIMPcontrolled visible light condition RGD 
SD-Tbc1d1Tn(sb)1FkhRatincreased muscle fatigability inducesIMPrunning on treadmill RGD 
Tbc1d1Ratincreased muscle fatigability inducesIMPrunning on treadmill RGD 
Tbc1d1Tn(sb)1FkhRatincreased muscle fatigability inducesIMPrunning on treadmill RGD 
SD-Tbc1d1Tn(sb)1FkhRatincreased oxygen consumption inducesIMPnucleoside/nucleotide RGD 
Tbc1d1Ratincreased oxygen consumption inducesIMPnucleoside/nucleotide RGD 
Tbc1d1Tn(sb)1FkhRatincreased oxygen consumption inducesIMPnucleoside/nucleotide RGD 
SD-Tbc1d1Tn(sb)1FkhRatincreased skeletal muscle glycogen level inducesIMPdirect electrical nerve stimulation RGD 
Tbc1d1Ratincreased skeletal muscle glycogen level inducesIMPdirect electrical nerve stimulation RGD 
Tbc1d1Tn(sb)1FkhRatincreased skeletal muscle glycogen level inducesIMPdirect electrical nerve stimulation RGD 
Objects Annotated

Genes (Rattus norvegicus)
Tbc1d1  (TBC1 domain family member 1)
Tbc1d1Tn(sb)1Fkh  (TBC1 domain family member 1; Sleeping Beauty induced mutant 1, Fkh)

Strains
SD-Tbc1d1Tn(sb)1Fkh  (NA)


Additional Information