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Molecular mechanism of insulin resistance

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Abstract

Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, leading to a reduced amount of IR protein in insulin target cells. PDK1-independent phosphorylation of PKCε causes this reduction in insulin receptor gene expression. One of the pathways through which fatty acid can induce insulin resistance in insulin target cells is suggested by these studies. We provide an overview of this important area, emphasizing the current status.

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Abbreviations

IDDM:

insulin-dependent diabetes mellitus

NIDDM:

non-insulin dependent diabetes mellitus

IR:

insulin receptor

FFA:

free fatty acid

IRS:

insulin receptor substrate

PI3 kinase:

phosphatidylinositol 3 phosphate kinase

PIP2 :

phosphatidylinositol 4,5 bisphosphate

DAG:

diacylglycerol

PDK1:

phosphoinositide-dependent kinase-1

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Correspondence to Samir Bhattacharya.

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Bhattacharya, S., Dey, D. & Roy, S.S. Molecular mechanism of insulin resistance. J Biosci 32, 405–413 (2007). https://doi.org/10.1007/s12038-007-0038-8

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