Article

Anti-Inflammatory Action of Insulin via Induction of Gadd45-β Transcription by the mTOR Signaling Pathway.

Department of Pathology, Division of Molecular and Cellular Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, 35294-0019.
Hepatic Medicine: Evidence and Research 06/2010; 2001(2):79-85. DOI: 10.2147/HMER.S7083
Source: PubMed

ABSTRACT Insulin regulates a large number of genes in a tissue-specific manner. We have identified genes modulated by insulin in the liver and in liver-derived cells that had not yet been characterized as insulin regulated, and these previous studies indicate that numerous genes are induced by insulin via the MEK-ERK pathway. We now describe new studies indicating that Gadd45-β can be induced by acute insulin treatment. Although other regulators of Gadd45-β expression may utilize the MEK-ERK pathway, the data indicate that insulin utilizes signaling pathways separate from either MEK-ERK, PI3-K or p38 signaling pathways in the regulation of Gadd45-β transcription. Our findings show that activation of a downstream effector of multiple signaling pathways, mTOR, was required for insulin-induction of Gadd45-β gene transcription. Increased expression of Gadd45-β can inhibit c-Jun N-terminal kinase (JNK) activity. Since TNFα is increased during inflammation, and acts, at least in part, via the JNK signaling pathway, insulin induction of Gadd45-β suggests a mechanism for the anti-inflammatory actions of insulin.

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May 27, 2014