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Göteborgs universitets publikationer

Saturated fatty acids inhibit induction of insulin gene transcription by JNK-mediated phosphorylation of insulin-receptor substrates

Författare och institution:
Giovanni Solinas (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); Willscott Naugler (-); Francesco Galimi (-); Myung-Shik Lee (-); Michael Karin (-)
Publicerad i:
Proceedings of the National Academy of Science of the United States of America, 103 ( 44 ) s. 16454-16459
ISSN:
0027-8424
E-ISSN:
1091-6490
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2006
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
JNKs are attractive targets for treatment of obesity and type-2 diabetes. A sustained increase in JNK activity was observed in dietary and genetic models of obesity in mice, whereas JNK deficiency prevented obesity-induced insulin resistance. A similar insulin-sensitizing effect was seen upon treatment of obese mice with JNK inhibitors. We now demonstrate that treatment with the saturated fatty acid palmitic acid results in sustained JNK activation and insulin resistance in primary mouse hepatocytes and pancreatic β-cells. In the latter, palmitic acid treatment inhibits glucose-induced insulin gene transcription, in part, by interfering with autocrine insulin signaling through phosphorylation of insulin-receptor substrates 1 and 2 at sites that interfere with binding to activated insulin receptors. This mechanism may account for the induction of central insulin resistance by free fatty acids.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Medicinska grundvetenskaper
Postens nummer:
241731
Posten skapad:
2016-09-13 16:45

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