Anti-inflammatory action of insulin via induction of Gadd45-β transcription by the mTOR signaling pathway


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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@inproceedings{Bortoff2010AntiinflammatoryAO, title={Anti-inflammatory action of insulin via induction of Gadd45-β transcription by the mTOR signaling pathway}, author={Katherine D Bortoff and Adam B. Keeton and John Lee Franklin and Joseph L. Messina}, booktitle={Hepatic medicine : evidence and research}, year={2010} }