| Chronic central leptin infusion modifies the response to acute central insulin injection by reducing the interaction of the insulin receptor with IRS2 and increasing its association with SOCS3. | |
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MedLine Citation:
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PMID: 21255014 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Leptin and insulin have overlapping intracellular signaling mechanisms and exert anorexigenic actions in the hypothalamus. We aimed to determine how chronic exposure to increased leptin affects the hypothalamic response to a rise in insulin. We analyzed the activation and interactions of components of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in the hypothalamus of rats treated icv for 14 days with leptin followed by a central injection of insulin and sacrificed 15 min later. Insulin increased glycemia and chronic leptin reduced this insulin induced rise in glucose. Leptin decreased the association between the insulin receptor beta chain (IRβ) and IRS2, augmented the association between Janus kinase 2 (JAK2) and IRS2, increased levels of the catalytic subunit of PI3K and pAkt-Ser473 and decreased FOXO1 levels. Insulin reduced the association between SOCS3 and IRβ, increased IRβ-IRS2 association and pAkt-Thr308 levels, with chronic leptin exposure blunting these effects. In conclusion, chronic exposure to leptin decreases the central response to insulin by increasing SOCS3 association to IR, which inhibits insulin signaling at the level of interaction of its receptor with IRS2 and activates PI3K by promoting JAK2-IRS2 association. Thus, these results suggest that this mechanism could be a target for the treatment of insulin resistance. |
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Authors:
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Emma Burgos-Ramos; Julie A Chowen; Eduardo Arilla-Ferreiro; Sandra Canelles; Jesús Argente; Vicente Barrios |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-22 |
Journal Detail:
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Title: Journal of neurochemistry Volume: - ISSN: 1471-4159 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Journal of Neurochemistry © 2011 International Society for Neurochemistry. |
Affiliation:
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Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto Investigación Sanitaria Princesa; Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009 Spain CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, E-28009 Spain Neurobiochemistry Unit, Department of Biochemistry and Molecular Biology, Medical School, Universidad de Alcalá, Alcalá de Henares, E-28871, Spain. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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