| Insulin receptor-independent upregulation of cellular glucose uptake. | |
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MedLine Citation:
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PMID: 22310476 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background:Cellular glucose uptake can be enhanced by upregulating Ras signaling in either insulin-dependent or -independent manner. In presence of insulin and intact insulin signaling, Ras has a negligible role in glucose uptake. Conversely, when insulin signaling is impaired in obesity or diabetes, the insulin-independent Ras pathway may be valuable for enhancing glucose disposal. We previously reported that Ad36, a human adenovirus, enhances cellular glucose uptake by upregulating the Ras/Glut4 pathway. Here, we investigated if Ad36-upregulated Ras via the insulin-independent pathway, to enhance glucose uptake. Furthermore, uncontrolled upregulation of Ras is linked with oncogenic cell transformation, if the tumor-suppressor gene p53 is also downregulated. Hence, we determined if upregulation of Ras by Ad36 would induce oncogenic cell transformation. Finally, we determined the relevance of Ad36 to insulin resistance in humans.Methods:Insulin receptor (IR) was knocked down with small interfering RNA in 3T3-L1 adipocytes, to determine if Ad36 increases the Ras/Glut4 pathway and glucose uptake without IR-signaling. Next, the effects of Ad36 on cell transformation and p53 abundance were determined. Finally, overweight or obese women were screened for seropositivity to Ad36, as an indicator of natural Ad36 infection. Associations of Ad36 infection with adiposity and C-reactive proteins (CRPs)-two key markers of insulin resistance, and with glucose disposal, were determined.Results:Unaffected by IR knock-down, Ad36 significantly increased the Ras pathway, Glut4 translocation and glucose uptake in 3T3-L1 adipocytes. Despite Ras upregulation, Ad36 did not transform 3T3-L1 cells. This may be because Ad36 significantly increased p53 protein in 3T3-L1 cells or mice adipose tissue. Ad36 seropositivity was associated with greater adiposity and CRP levels, yet a significantly higher systemic glucose disposal rate.Conclusions:Overall, the study offers Ras/Glut4 pathway as an alternate to enhance glucose disposal when insulin signaling is impaired, and, importantly, provides Ad36 as a tool to understand the modulation of that pathway.International Journal of Obesity advance online publication, 7 February 2012; doi:10.1038/ijo.2012.6. |
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Authors:
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R Krishnapuram; H Kirk-Ballard; E J Dhurandhar; O Dubuisson; V Messier; R Rabasa-Lhoret; V Hegde; S Aggarwal; N V Dhurandhar |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-07 |
Journal Detail:
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Title: International journal of obesity (2005) Volume: - ISSN: 1476-5497 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101256108 Medline TA: Int J Obes (Lond) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Infections and Obesity Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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