Anti-Inflammatory Action of Insulin via Induction of Gadd45-β Transcription by the mTOR Signaling Pathway
| Autor: | J. Lee Franklin, Katherine D. Bortoff, Joseph L. Messina, Adam B. Keeton |
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| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
insulin medicine.medical_treatment p38 mitogen-activated protein kinases p38 Internal medicine medicine PI3K/AKT/mTOR pathway Original Research Gadd45–β Hepatology biology Kinase Effector Gadd45 Insulin PI3-kinase Cell biology Insulin receptor ERK Endocrinology biology.protein mTOR JNK Signal transduction Evidence and Research [Hepatic Medicine] |
| Zdroj: | Hepatic Medicine : Evidence and Research |
| ISSN: | 1179-1535 |
| Popis: | Katherine D Bortoff1, Adam B Keeton1, J Lee Franklin1, Joseph L Messina1,21Department of Pathology, Division of Molecular and Cellular Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, USA; 2Veterans Affairs Medical Center, Birmingham, Alabama, USAAbstract: Insulin regulates a large number of genes in a tissue-specific manner. We have previously identified genes modulated by insulin in the liver and in liver-derived cells that have not yet been characterized as insulin regulated, and results of these previous studies indicated 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.Keywords: insulin, Gadd45−β, mTOR, ERK, PI3-kinase, p38, JNK |
| Databáze: | OpenAIRE |
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