| First Author | Dey D | Year | 2007 |
| Journal | Biochem Biophys Res Commun | Volume | 357 |
| Issue | 2 | Pages | 474-9 |
| PubMed ID | 17434141 | Mgi Jnum | J:122347 |
| Mgi Id | MGI:3714100 | Doi | 10.1016/j.bbrc.2007.03.183 |
| Citation | Dey D, et al. (2007) Fatty acid represses insulin receptor gene expression by impairing HMGA1 through protein kinase Cepsilon. Biochem Biophys Res Commun 357(2):474-9 |
| abstractText | 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 PKCepsilon was also inhibited. Surprisingly, phosphorylation of cytosolic PKCepsilon 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 PKCepsilon translocation inhibitor peptide, epsilonV1, suppressed this inhibitory effect of palmitate, suggesting requirement of phospho-PKCepsilon migration to implement palmitate effect. Experimental evidences indicate that phospho-PKCepsilon 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. |
