Calorie Restriction-Induced Increase in Skeletal Muscle Insulin Sensitivity Is Not Prevented by Overexpression of the p55α Subunit of Phosphoinositide 3-Kinase

Frontiers in Physiology
Vitor F MartinsCarrie E McCurdy

Abstract

Introduction: The Phosphoinositide 3-kinase (PI3K) signaling pathway plays an important role in skeletal muscle insulin-stimulated glucose uptake. While whole-body and tissue specific knockout (KO) of individual or combinations of the regulatory subunits of PI3K (p85α, p55α, and p50α or p85β); increase insulin sensitivity, no study has examined whether increasing the expression of the individual regulatory subunits would inhibit insulin action in vivo. Therefore, the objective of this study was to determine whether skeletal muscle-specific overexpression of the p55α regulatory subunit of PI3K impairs skeletal muscle insulin sensitivity, or prevents its enhancement by caloric restriction. Methods: We developed a novel "floxed" mouse that, through the Cre-LoxP approach, allows for tamoxifen (TMX)-inducible and skeletal muscle-specific overexpression of the p55α subunit of PI3K (referred to as, 'p55α-mOX'). Beginning at 10 weeks of age, p55α-mOX mice and their floxed littermates (referred to as wildtype [WT]) either continued with free access to food (ad libitum; AL), or were switched to a calorie restricted diet (CR; 60% of AL intake) for 20 days. We measured body composition, whole-body energy expenditure, oral glucose tolerance...Continue Reading

References

May 1, 1990·Metabolism: Clinical and Experimental·R C BonadonnaR A DeFronzo
May 1, 1983·Proceedings of the Society for Experimental Biology and Medicine·J B ClarkW N Shaw
Jun 1, 1983·The Journal of Clinical Investigation·R I FinkJ M Olefsky
Jun 1, 1983·The Journal of Clinical Investigation·J W RoweJ S Flier
Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·Kohjiro UekiLewis C Cantley
Dec 26, 2001·Science's STKE : Signal Transduction Knowledge Environment·K Okkenhaug, B Vanhaesebroeck
Jan 10, 2002·The Journal of Clinical Investigation·Franck Mauvais-JarvisC Ronald Kahn
Dec 16, 2003·Molecular and Cellular Biology·Dong ChenC Ronald Kahn
Dec 23, 2004·American Journal of Physiology. Endocrinology and Metabolism·Carrie E McCurdyGregory D Cartee
Mar 29, 2005·Nature Cell Biology·Kathrine AbellChristine J Watson
Apr 9, 2005·Trends in Biochemical Sciences·Bart VanhaesebroeckLazaros C Foukas
Aug 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·Cullen M TaniguchiC Ronald Kahn
May 2, 2007·Proceedings of the National Academy of Sciences of the United States of America·Barbara GeeringBart Vanhaesebroeck
Mar 10, 2011·American Journal of Physiology. Endocrinology and Metabolism·Naveen SharmaGregory D Cartee
Sep 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Barbara BecattiniGiovanni Solinas
Oct 12, 2011·The Journal of Clinical Investigation·Simon SchenkJerrold M Olefsky
May 9, 2012·Skeletal Muscle·John J McCarthyKaryn A Esser
Apr 3, 2014·American Journal of Physiology. Endocrinology and Metabolism·Victoria L B NelsonRichard Z Lin
Jun 7, 2014·Cell Death and Differentiation·S PensaC J Watson
Jul 30, 2015·ELife·Lydia W T CheungGordon B Mills
Dec 30, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Samuel A LaBargeSimon Schenk

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Citations

Feb 28, 2020·Journal of Applied Physiology·C Brooks MobleyJohn J McCarthy
Mar 20, 2019·American Journal of Physiology. Endocrinology and Metabolism·Vitor F MartinsSimon Schenk

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BETA
PCR
ELISA
transgenic

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Image Lab
Prism
GraphPad

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