title: Anti-Inflammatory Action of Insulin via Induction of Gadd45-β Transcription by the mTOR Signaling Pathway.
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.
authors.affiliation: Department of Pathology, Division of Molecular and Cellular Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, 35294-0019.
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Bortoff
authors.forename: Adam B
authors.initials: AB
authors.lastname: Keeton
authors.forename: J Lee
authors.initials: JL
authors.lastname: Franklin
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Messina