Fatty acid Represses Insulin Receptor Gene Expression by Impairing HMGA1 through Protein Kinase Ce
EPrints@IICB
View Archive InfoField | Value | |
Title |
Fatty acid Represses Insulin Receptor Gene Expression by Impairing HMGA1 through Protein Kinase Ce
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Creator |
Dey, Debleena
Bhattacharya, Anirban Roy, Sib Sankar Bhattacharya, Samir |
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Subject |
Cell Biology & Physiology
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Description |
It is known that free fatty acid (FFA) contributes to the development of insulin resistance and type2 diabetes. However, the underlying mechanism in FFA-induced insulin resistance is still unclear. In the present investigation we have demonstrated that palmitate significantly (p < 0.001) inhibited insulin-stimulated phosphorylation of PDK1, the key insulin signaling molecule. Consequently, PDK1 phosphorylation of plasma membrane bound PKCe was also inhibited. Surprisingly, phosphorylation of cytosolic PKCe was greatly stimulated by palmitate; this was then translocated to the nuclear region and associated with the inhibition of insulin receptor (IR) gene transcription. A PKCe translocation inhibitor peptide, eV1, suppressed this inhibitory effect of palmitate, suggesting requirement of phospho-PKCe migration to implement palmitate effect. Experimental evidences indicate that phospho-PKCe adversely affected HMGA1. Since HMGA1 regulates IR promoter activity, expression of IR gene was impaired causing reduction of IR on cell surface and that compromises with insulin sensitivity. |
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Date |
2007
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://www.eprints.iicb.res.in/1047/1/BIOCHEMICAL_AND_BIOPHYSICAL_RESEARCH_COMMUNICATIONS__357(_2)_474%2D479;2007[79].pdf
Dey, Debleena and Bhattacharya, Anirban and Roy, Sib Sankar and Bhattacharya, Samir (2007) Fatty acid Represses Insulin Receptor Gene Expression by Impairing HMGA1 through Protein Kinase Ce. Biochemical and Biophysical Research Communications, 357 (2). pp. 474-479. |
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Relation |
http://dx.doi.org/10.1016/j.bbrc.2007.03.183
http://www.eprints.iicb.res.in/1047/ |
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