RGD Reference Report - Lipoic acid increases heat shock protein expression and inhibits stress kinase activation to improve insulin signaling in skeletal muscle from high-fat-fed rats. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Lipoic acid increases heat shock protein expression and inhibits stress kinase activation to improve insulin signaling in skeletal muscle from high-fat-fed rats.

Authors: Gupte, AA  Bomhoff, GL  Morris, JK  Gorres, BK  Geiger, PC 
Citation: Gupte AA, etal., J Appl Physiol (1985). 2009 Apr;106(4):1425-34. doi: 10.1152/japplphysiol.91210.2008. Epub 2009 Jan 29.
RGD ID: 7495775
Pubmed: PMID:19179648   (View Abstract at PubMed)
DOI: DOI:10.1152/japplphysiol.91210.2008   (Journal Full-text)

The antioxidant alpha-lipoic acid (LA) has been shown to improve insulin action in high-fat (HF)-fed animal models, yet little is known about its underlying mechanisms of action. We hypothesize that LA acts by inducing heat shock proteins (HSPs), which then inhibit stress kinases known to interfere with insulin signaling intermediates. Male Wistar rats were fed a HF diet (60% calories from fat) for 6 wk, while controls received a chow diet (10% calories from fat). One-half of the rats in each group received daily LA injections (30 mg/kg body wt). In rats fed a HF diet, LA increased expression of HSP72 and activation of HSP25 in soleus muscle, but it had no effect on HSPs in muscle from chow-fed rats. LA treatment reduced phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and inhibitor of kappaB kinase-beta (IKKbeta) activity (IkappaBalpha protein levels) in rats fed a HF diet and effectively restored insulin responsiveness, as seen by insulin-stimulated phosphorylated Akt/Akt and 2-deoxyglucose uptake in soleus muscle. LA also induced activation of p38 MAPK and AMP-activated protein kinase, proteins previously implicated in insulin-independent glucose uptake. In addition, acute LA treatment induced HSPs in vitro in L6 muscle cells and prevented the activation of JNK and IKKbeta with stimulants such as anisomycin and TNF-alpha, respectively. In conclusion, our results suggest chronic LA treatment results in stress kinase inhibition and improved insulin signaling through a HSP-mediated mechanism.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to fatty acid  IEP 7495775 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ikbkb  (inhibitor of nuclear factor kappa B kinase subunit beta)


Additional Information