References
Query Results -- Details
MGI Accession ID: MGI:1861910
J Number: J:63895
Other Accession IDs:
Title: Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice.
Authors: Shimomura I; Matsuda M; Hammer RE; Bashmakov Y; Brown MS; Goldstein JL
Journal: Mol Cell
Volume: 6
Issue: 1
Date: 2000 Jul
Year: 2000
Pages: 77-86
Review Status: Peer Reviewed
Abstract:
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 IRS-2 deficiency, insulin continues to stimulate production of SREBP-1c, a transcription factor that activates fatty acid synthesis. The combination of insulin resistance (inappropriate gluconeogenesis) and insulin sensitivity (elevated lipogenesis) establishes a vicious cycle that aggravates hyperinsulinemia and insulin resistance in lipodystrophic and ob/ob mice.
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