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Title: Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics
Authors: Coelho, Margarida 
Nunes, Patricia
Mendes, Vera M. 
Manadas, Bruno 
Heerschap, Arend
Jones, John G. 
Issue Date: 2015
Publisher: Hindawi
Project: The authors acknowledge financial support from Fundac¸˜ao paraaCiˆencia e Tecnologia, Portugal (FCT) (ResearchGrants PTDC/SAU-MET/111398/2009 and EXCL/DTP-PIC/0069/ 2012), the Center for Translational Molecular Medicine consortium, Netherlands (CTMM) (Research Grant PREDDICt (Grant 01C-104)), structural funding for the Rede Nacional de Espectrometria de Massa (RNEM) (Research Grant RNEM (REDE/1506/REM/2005)), and the Center of Neuroscience and Cell Biology, University of Coimbra, Portugal (Research Grant PEst-C/SAU/LA0001/2013-2014). This project is also cofunded by the European Regional Development Fund (FEDER) through the programme COMPETE, Operational Competitiveness Programme. The authors also acknowledge insightful discussions of the paper with Matthijs Hesselink of Maastricht University. Strategic Project UID/NED/04539/2013 is also acknowledged. 
Serial title, monograph or event: Journal of Diabetes Research
Volume: 2015
Abstract: Mice deficient in adipose triglyceride lipase (ATGL(-/-)) present elevated ectopic lipid levels but are paradoxically glucose-tolerant. Measurement of endogenous glucose production (EGP) and Cori cycle activity provide insights into the maintenance of glycemic control in these animals. These parameters were determined in 7 wild-type (ATGL(+/-)) and 6 ATGL(-/-) mice by a primed-infusion of [U-(13)C6]glucose followed by LC-MS/MS targeted mass-isotopomer analysis of blood glucose. EGP was quantified by isotope dilution of [U-(13)C6]glucose while Cori cycling was estimated by analysis of glucose triose (13)C-isotopomers. Fasting plasma free fatty-acids were significantly lower in ATGL(-/-) versus control mice (0.43 ± 0.05 mM versus 0.73 ± 0.11 mM, P < 0.05). Six-hour fasting EGP rates were identical for both ATGL(-/-) and control mice (79 ± 11 versus 71 ± 7 μmol/kg/min, resp.). Peripheral glucose metabolism was dominated by Cori cycling (80 ± 2% and 82 ± 7% of glucose disposal for ATGL(-/-) and control mice, resp.) indicating that peripheral glucose oxidation was not significantly upregulated in ATGL(-/-) mice under these conditions. The glucose (13)C-isotopomer distributions in both ATGL(-/-) and control mice were consistent with extensive hepatic pyruvate recycling. This suggests that gluconeogenic outflow from the Krebs cycle was also well compensated in ATGL(-/-) mice.
ISSN: 2314-6745
DOI: 10.1155/2015/542029
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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