| Resistance to trophic neurite outgrowth of sensory neurons exposed to insulin. | |
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MedLine Citation:
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PMID: 22303986 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Insulin offers trophic support through receptors expressed widely on peripheral neurons. In this work, we studied whether peripheral sensory neurons demonstrate resistance to its trophic properties, a property relevant during type 2 diabetes mellitus or following supraphysiological therapy. Insulin receptors (IRs) were not only localized to neuronal membranes and cytoplasm but also had a unique, previously unrecognized localization to neuronal nuclei. We confirmed that nanomolar doses increased neurite outgrowth of adult sensory neurons, but in response to micromolar doses of insulin, even following a brief two hour exposure, survival and outgrowth of neurites were blunted. Neurons exposed to picomolar insulin concentrations in their media for 5d had resistance to the impact of later nanomolar doses of insulin. Using a stripe assay seeded with insulin, neurites were more likely to reject higher doses of insulin. Insulin downregulated mRNAs of the IRβ subunit and upregulated levels of GSK-3β, both potential mechanisms of insulin resistance, while downregulating the protein expression of pAkt and pGSK-3β. Overall these studies identify neuronal nuclear targeting of insulin and evidence for insulin induced resistance to its trophic properties. The findings have implications for the understanding of the actions of insulin in the treatment of diabetes and neurological disorders. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry. |
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Authors:
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Bhagat Singh; Yongqin Xu; Todd McLaughlin; Vandana Singh; Jose A Martinez; Anand Krishnan; Douglas W Zochodne |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-3 |
Journal Detail:
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Title: Journal of neurochemistry Volume: - ISSN: 1471-4159 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-6 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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© 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry. |
Affiliation:
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Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada Salk Institute for Biological Studies, La Jolla, CA, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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