Dey, Debleena ; Mukherjee, Mohua ; Basu, Dipanjan ; Datta, Malabika ; Roy, Sib Sankar ; Bandyopadhyay, Arun ; Bhattacharya, Samir (2005) Inhibition of insulin receptor gene expression and insulin signaling by fatty acid: interplay of PKC isoforms therein Cellular Physiology and Biochemistry, 16 (4-6). pp. 217-228. ISSN 1015-8987
![]()
|
PDF
- Publisher Version
1MB |
Official URL: http://content.karger.com/ProdukteDB/produkte.asp?...
Related URL: http://dx.doi.org/10.1159/000089847
Abstract
Fatty acids are known to play a key role in promoting the loss of insulin sensitivity causing insulin resistance and type 2 diabetes. However, underlying mechanism involved here is still unclear. Incubation of rat skeletal muscle cells with palmitate followed by I125- insulin binding to the plasma membrane receptor preparation demonstrated a two-fold decrease in receptor occupation. In searching the cause for this reduction, we found that palmitate inhibition of insulin receptor (IR) gene expression effecting reduced amount of IR protein in skeletal muscle cells. This was followed by the inhibition of insulin-stimulated IRβ tyrosine phosphorylation that consequently resulted inhibition of insulin receptor substrate 1 (IRS 1) and IRS 1 associated phosphatidylinositol-3 kinase (PI3 Kinase), phosphoinositide dependent kinase-1 (PDK 1) phosphorylation. PDK 1 dependent phosphorylation of PKCζ and Akt/PKB were also inhibited by palmitate. Surprisingly, although PKCε phosphorylation is PDK1 dependent, palmitate effected its constitutive phosphorylation independent of PDK1. Time kinetics study showed translocation of palmitate induced phosphorylated PKCε from cell membrane to nuclear region and its possible association with the inhibition of IR gene transcription. Our study suggests one of the pathways through which fatty acid can induce insulin resistance in skeletal muscle cell.
Item Type: | Article |
---|---|
Source: | Copyright of this article belongs to Karger Publisher. |
ID Code: | 21557 |
Deposited On: | 22 Nov 2010 06:47 |
Last Modified: | 17 May 2016 05:45 |
Repository Staff Only: item control page