Inhibition of Insulin Receptor Gene Expression and Insulin Signaling by Fatty Acid: Interplay of PKC Isoforms Therein
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Inhibition of Insulin Receptor Gene Expression
and Insulin Signaling by Fatty Acid: Interplay of
PKC Isoforms Therein
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| Creator |
Dey, Debleena
Mukherjee, Mohua Basu, Dipanjan Datta, Malabika Roy, Sib Sankar Bandyopadhyay , Arun Bhattacharya, Samir |
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| Subject |
Cell Biology & Physiology
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| Description |
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.
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| Publisher |
Karger
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| Date |
2005
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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/569/1/CELLULAR_PHYSIOLOGY_AND_BIOCHEMISTRY_16(_4%2D6)_217%2D228_;2005[116].pdf
Dey, Debleena and Mukherjee, Mohua and Basu, Dipanjan and Datta, Malabika and Roy, Sib Sankar and Bandyopadhyay , Arun and 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. |
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| Relation |
http://dx.doi.org/10.1159/000089847
http://www.eprints.iicb.res.in/569/ |
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