Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice.

@article{Shimomura2000DecreasedIA,
  title={Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice.},
  author={Iichiro Shimomura and Mami Matsuda and Robert Hammer and Yuriy K Bashmakov and Michael Scott Brown and Joseph L Goldstein},
  journal={Molecular cell},
  year={2000},
  volume={6 1},
  pages={77-86}
}
In mice with too little fat (lipodystrophy) or too much fat (ob/ob), leptin deficiency leads to hyperglycemia, hyperinsulinemia, and insulin resistance. In both disorders, the liver overproduces glucose as a result of resistance to the normal action of insulin in repressing mRNAs for gluconeogenic enzymes. Here we show that chronic hyperinsulinemia downregulates the mRNA for IRS-2, an essential component of the insulin-signaling pathway in liver, thereby producing insulin resistance. Despite… CONTINUE READING
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