RGD Reference Report - mTOR partly mediates insulin resistance by phosphorylation of insulin receptor substrate-1 on serine(307) residues after burn. - Rat Genome Database

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mTOR partly mediates insulin resistance by phosphorylation of insulin receptor substrate-1 on serine(307) residues after burn.

Authors: Xin-Long, C  Zhao-Fan, X  Dao-Feng, B  Wei, D 
Citation: Xin-Long C, etal., Burns. 2011 Feb;37(1):86-93. doi: 10.1016/j.burns.2010.04.005. Epub 2010 Jul 1.
RGD ID: 10041043
Pubmed: PMID:20594757   (View Abstract at PubMed)
DOI: DOI:10.1016/j.burns.2010.04.005   (Journal Full-text)

Mammalian target of rapamycin (mTOR) is an important mediator for cross talk between nutritional signals and metabolic signals of insulin by downregulating insulin receptor substrate proteins. Therefore, mTOR inhibition could become a therapeutic strategy in insulin-resistant states, including insulin resistance induced by burn. We tested this hypothesis in the rat model of 30% TBSA full thickness burn, using the mTOR inhibitor rapamycin. Rapamycin (0.4 mg/kg, i.p.) was injected 2 h before euglycemic-hyperinsulinemic glucose clamps at 4 days after burn. IRS-1, phospho-serine(3)(0)(7), phospho-tyrosine of IRS-1 and phospho-mTOR in muscle tissue were determined by immunoprecipitation and Western blot analysis or immunohistochemistry. Plasma TNF-alpha, insulin and C-peptide were determined before and after euglycemic-hyperinsulinemic glucose clamps. Our data showed that TNF-alpha, insulin and C-peptide significantly increased in the early stage after burn (P < 0.01). The infused rates of total 10% glucose (GIR, mg/kg min) significantly decreased at 4 days after burn. The level of IRS-1 serine(3)(0)(7) phosphorylation in muscle in vivo significantly increased after burn (P < 0.01), while insulin-induced tyrosine phosphorylation of IRS-1 significantly decreased (P < 0.01). Inhibition of mTOR by rapamycin inhibited the phosphorylation of mTOR, reduced serine(3)(0)(7) phosphorylation, elevated tyrosine phosphorylation and partly prevented the decrease of GIR after burn. However, TNF-alpha, insulin and C-peptide were not decreased by rapamycin treatment postburn. Taken together, these results indicate that the mTOR pathway is an important modulator of the signals involved in the acute regulation of insulin-stimulated glucose metabolism, and at least, partly contributes to burn-induced insulin resistance. mTOR inhibition may become a therapeutic strategy in insulin-resistant states after burn.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Burns  ISOMtor (Rattus norvegicus)10041043; 10041043protein:increased serine phosphorylation:skeletal muscleRGD 
Burns  IDA 10041043protein:increased serine phosphorylation:skeletal muscleRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mtor  (mechanistic target of rapamycin kinase)

Genes (Mus musculus)
Mtor  (mechanistic target of rapamycin kinase)

Genes (Homo sapiens)
MTOR  (mechanistic target of rapamycin kinase)


Additional Information