Development of glucose intolerance in male transgenic mice overexpressing human glycogen synthase kinase-3beta on a muscle-specific promoter

Metabolism: Clinical and Experimental
N J PearceJ C Holder

Abstract

Glycogen synthase kinase-3 (GSK-3) protein levels and activity are elevated in skeletal muscle in type 2 diabetes, and inversely correlated with both glycogen synthase activity and insulin-stimulated glucose disposal. To explore this relationship, we have produced transgenic mice that overexpress human GSK-3beta in skeletal muscle. GSK-3beta transgenic mice were heavier, by up to 20% (P < .001), than their age-matched controls due to an increase in fat mass. The male GSK-3beta transgenic mice had significantly raised plasma insulin levels and by 24 weeks of age became glucose-intolerant as determined by a 50% increase in the area under their oral glucose tolerance curve (P < .001). They were also hyperlipidemic with significantly raised serum cholesterol (+90%), nonesterified fatty acids (NEFAs) (+55%), and triglycerides (+170%). At 29 weeks of age, GSK-3beta protein levels were 5-fold higher, and glycogen synthase activation (-27%), glycogen levels (-58%) and insulin receptor substrate-1 (IRS-1) protein levels (-67%) were significantly reduced in skeletal muscle. Hepatic glycogen levels were significantly increased 4-fold. Female GSK-3beta transgenic mice did not develop glucose intolerance despite 7-fold overexpression of GSK...Continue Reading

References

Nov 1, 1992·The Journal of Clinical Investigation·M J SaadC R Kahn
Mar 1, 1992·Diabetes Care·R A DeFronzoE Ferrannini
Mar 1, 1992·Diabetes Care·H Beck-NielsenP Thye-Rønn
Aug 1, 1974·Analytical Biochemistry·J V Passonneau, V R Lauderdale
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·J ManchesterJ C Lawrence
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·H Eldar-Finkelman, E G Krebs
Mar 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·W H MartinJ L Treadway
Jan 22, 2000·The Journal of Clinical Investigation·Y KidoD Accili
Mar 27, 2001·Bioorganic & Medicinal Chemistry Letters·D G SmithR W Ward
May 15, 2001·Biochemical and Biophysical Research Communications·G B MooreJ C Clapham
Apr 12, 2002·Journal of Cellular Biochemistry·David Hartley, Geoffrey M Cooper
May 29, 2002·Diabetes·Andrea HevenerJerrold Olefsky
Jan 9, 2003·American Journal of Physiology. Endocrinology and Metabolism·Erik J HenriksenStephen D Harrison
Oct 31, 2003·IUBMB Life·Carsten Schmitz-Peiffer, Jonathan P Whitehead

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Citations

Jul 20, 2012·Molecular and Cellular Biochemistry·Harlokesh Narayan YadavPyare Lal Sharma
Sep 1, 2006·Neurochemical Research·Richard S JopeEléonore Beurel
Sep 24, 2005·The Journal of Biological Chemistry·Buffie Clodfelder-MillerRichard S Jope
Aug 13, 2008·Molecular and Cellular Biology·Satish PatelJames R Woodgett
Sep 11, 2008·Expert Opinion on Therapeutic Targets·Katrina MacAulay, James R Woodgett
Dec 18, 2010·Journal of Molecular and Cellular Cardiology·Hui ChengThomas Force
Jul 6, 2010·European Journal of Pharmacology·Harlokesh Narayan YadavPyare Lal Sharma
Jun 10, 2009·Molecular and Cellular Endocrinology·T P CiaraldiR R Henry
Apr 19, 2005·Obesity Research·Louis PérusseClaude Bouchard
Apr 16, 2009·British Journal of Pharmacology·Geetha Vani RayasamAbhijit Ray
Jun 3, 2006·Obesity·Tuomo RankinenClaude Bouchard
Apr 24, 2010·Journal of Cellular and Molecular Medicine·Lee-Anne StantonFrank Beier
Jul 24, 2015·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Akilavalli NarasimhanBalasubramanian Karundevi
Jan 18, 2012·The Biochemical Journal·Peter J RoachVincent S Tagliabracci
Oct 3, 2007·Cell Metabolism·Katrina MacAulayJames R Woodgett
Jun 7, 2017·Journal of Alzheimer's Disease : JAD·Kevin HuynhPeter J Meikle
Sep 1, 2006·Journal of the American Society of Nephrology : JASN·Chun-Liang LinFeng-Sheng Wang
Jan 28, 2012·Molecular Endocrinology·Michael A PearenGeorge E O Muscat
Feb 16, 2006·American Journal of Physiology. Endocrinology and Metabolism·Betsy B Dokken, Erik J Henriksen
Jun 8, 2006·American Journal of Physiology. Endocrinology and Metabolism·Theodore P CiaraldiRobert R Henry
Jan 27, 2005·American Journal of Physiology. Endocrinology and Metabolism·Betsy B DokkenErik J Henriksen
Jul 18, 2019·GeroScience·Dylan C Souder, Rozalyn M Anderson
Aug 20, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Chethan SampathPandu R Gangula
Aug 5, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jiongjie JingLihua Lyu
Feb 25, 2017·The Journal of Endocrinology·Sergio Di MeoPaola Venditti
Jun 1, 2010·Molecular and Cellular Biochemistry·Harlokesh Narayan YadavP L Sharma

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