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Journal of Diabetes Research
Volume 2015, Article ID 542029, 8 pages
Research Article

Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics

1CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
2MRC National Institute for Medical Research, London, UK
3Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
4Portuguese Diabetes Association (APDP), Lisbon, Portugal

Received 26 January 2015; Accepted 8 June 2015

Academic Editor: Ute Christine Rogner

Copyright © 2015 Margarida Coelho et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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-13C6]glucose followed by LC-MS/MS targeted mass-isotopomer analysis of blood glucose. EGP was quantified by isotope dilution of [U-13C6]glucose while Cori cycling was estimated by analysis of glucose triose 13C-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, ). 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 13C-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.