Effects of DEHP and its metabolite MEHP on insulin signalling and proteins involved in GLUT4 translocation in cultured L6 myotubes

Graphical abstract Legend for concept diagram. A proposed schematic diagram to show the effect of DEHP and MEHP on insulin signalling molecules and GLUT4 translocation in L6 myotubes. Downregulated proteins are represented as in different color for DEHP (red) and MEHP (blue). Upregulated proteins ar...

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Bibliographic Details
Published in:Toxicology (Amsterdam) 2017-07, Vol.386, p.60-71
Main Authors: Viswanathan, Mangala Priya, Mullainadhan, Vigneswari, Chinnaiyan, Mayilvanan, Karundevi, Balasubramanian
Format: Article
Language:English
Subjects:
Animals
Blood Glucose - drug effects
Cell Membrane - metabolism
Cells, Cultured
DEHP
Deoxyglucose - metabolism
Diethylhexyl Phthalate - administration & dosage
Diethylhexyl Phthalate - analogs & derivatives
Diethylhexyl Phthalate - toxicity
Dose-Response Relationship, Drug
Emergency
Glucose Transporter Type 4 - metabolism
GLUT4
Glycogen - metabolism
Insulin - metabolism
Insulin resistance
Insulin signalling
MEHP
Muscle Fibers, Skeletal - drug effects
Muscle Fibers, Skeletal - metabolism
Muscle, Skeletal - drug effects
Plasticizers - administration & dosage
Plasticizers - toxicity
Rats
Signal Transduction - drug effects
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Summary:Graphical abstract Legend for concept diagram. A proposed schematic diagram to show the effect of DEHP and MEHP on insulin signalling molecules and GLUT4 translocation in L6 myotubes. Downregulated proteins are represented as in different color for DEHP (red) and MEHP (blue). Upregulated proteins are indicated as . GLUT4 translocation during insulin – stimulated condition is represented in the figure. – GLUT4 Storage Vesicle, – GLUT4, – VAMP2, – IRAP, – Syntaxin 4. Re-orientation of Munc 18c during insulin-stimulated condition is represented in the figure. Insulin signalling molecules (IR, pIRTyr1162/1163 , IRS1, pIRS1Tyr632 , pAktTyr315 , pAktSer473 , pAktThr308 , AS160, pAS160Thr642 , Rab8A, Rab13, GSK3β and pGSK3βSer9 as well as GLUT4 (cytosol and plasma membrane) proteins were found to be decreased. Proteins involved in GLUT4 translocation such as Syntaxin-4, Synip, SNAP-23 (plasma membrane) were found to be decreased upon DEHP and MEHP treatment whereas Munc18c and SNAP23 (cytosol) proteins were significantly increased upon DEHP treatment and decreased upon MEHP treatment.
ISSN:0300-483X
1879-3185
DOI:10.1016/j.tox.2017.05.005