Deficiency of Phosphoinositide 3-Kinase Enhancer Protects Mice From Diet-Induced Obesity and Insulin Resistance

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Deficiency of Phosphoinositide 3-Kinase Enhancer Protects Mice From Diet-Induced Obesity and Insulin Resistance

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dc.contributor.author Jung, Dae Young
dc.contributor.author Jun, John Y.
dc.contributor.author Kim, Jason K.
dc.contributor.author Ye, Keqiang
dc.contributor.author Chan, Chi Bun
dc.contributor.author Liu, Xia
dc.contributor.author Luo, Hongbo
dc.date.accessioned 2011-09-21T17:19:00Z
dc.date.issued 2010
dc.identifier.citation Chan, Chi Bun, Xia Liu, Dae Young Jung, John Y. Jun, Hongbo R. Luo, Jason K. Kim, and Keqiang Ye. 2010. Deficiency of phosphoinositide 3-kinase enhancer protects mice from diet-induced obesity and insulin resistance. Diabetes 59(4): 883-893. en_US
dc.identifier.issn 0012-1797 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5136952
dc.description.abstract OBJECTIVE: Phosphoinositide 3-kinase enhancer A (PIKE-A) is a proto-oncogene that promotes tumor growth and transformation by enhancing Akt activity. However, the physiological functions of PIKE-A in peripheral tissues are unknown. Here, we describe the effect of PIKE deletion in mice and explore the role of PIKE-A in obesity development. RESEARCH DESIGN AND METHODS: Whole-body PIKE knockout mice were generated and subjected to high-fat–diet feeding for 20 weeks. The glucose tolerance, tissue-specific insulin sensitivity, adipocyte differentiation, and lipid oxidation status were determined. The molecular mechanism of PIKE in the insulin signaling pathway was also studied. RESULTS: We show that PIKE-A regulates obesity development by modulating AMP-activated protein kinase (AMPK) phosphorylation. PIKE-A is important for insulin to suppress AMPK phosphorylation. The expression of PIKE-A is markedly increased in adipose tissue of obese mice, whereas depletion of PIKE-A inhibits adipocyte differentiation. PIKE knockout mice exhibit a prominent phenotype of lipoatrophy and are resistant to high-fat diet–induced obesity, liver steatosis, and diabetes. PIKE knockout mice also have augmented lipid oxidation, which is accompanied by enhanced AMPK phosphorylation in both muscle and adipose tissue. Moreover, insulin sensitivity is improved in PIKE-A–deficient muscle and fat, thus protecting the animals from diet-induced diabetes. CONCLUSIONS: Our results suggest that PIKE-A is implicated in obesity and associated diabetes development by negatively regulating AMPK activity. en_US
dc.language.iso en_US en_US
dc.publisher American Diabetes Association en_US
dc.relation.isversionof doi:10.2337/db09-1404 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844836/pdf/ en_US
dash.license LAA
dc.subject obesity studies en_US
dc.title Deficiency of Phosphoinositide 3-Kinase Enhancer Protects Mice From Diet-Induced Obesity and Insulin Resistance en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Diabetes en_US
dash.depositing.author Luo, Hongbo
dc.date.available 2011-09-21T17:19:00Z
dash.affiliation.other 103565 en_US

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