Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics
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 parameter...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/542029 |
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| author | Margarida Coelho Patricia Nunes Vera M. Mendes Bruno Manadas Arend Heerschap John G. Jones |
| author_facet | Margarida Coelho Patricia Nunes Vera M. Mendes Bruno Manadas Arend Heerschap John G. Jones |
| author_sort | Margarida Coelho |
| collection | DOAJ |
| description | 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, 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 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. |
| format | Article |
| id | doaj-art-b9a30e8aa26341e38f97ae92eb93300c |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
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| series | Journal of Diabetes Research |
| spelling | doaj-art-b9a30e8aa26341e38f97ae92eb93300c2025-02-03T05:58:07ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/542029542029Effect of Global ATGL Knockout on Murine Fasting Glucose KineticsMargarida Coelho0Patricia Nunes1Vera M. Mendes2Bruno Manadas3Arend Heerschap4John G. Jones5CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, PortugalMRC National Institute for Medical Research, London, UKCNC—Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, PortugalDepartment of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, NetherlandsCNC—Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, PortugalMice 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, 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 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.http://dx.doi.org/10.1155/2015/542029 |
| spellingShingle | Margarida Coelho Patricia Nunes Vera M. Mendes Bruno Manadas Arend Heerschap John G. Jones Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics Journal of Diabetes Research |
| title | Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics |
| title_full | Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics |
| title_fullStr | Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics |
| title_full_unstemmed | Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics |
| title_short | Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics |
| title_sort | effect of global atgl knockout on murine fasting glucose kinetics |
| url | http://dx.doi.org/10.1155/2015/542029 |
| work_keys_str_mv | AT margaridacoelho effectofglobalatglknockoutonmurinefastingglucosekinetics AT patricianunes effectofglobalatglknockoutonmurinefastingglucosekinetics AT verammendes effectofglobalatglknockoutonmurinefastingglucosekinetics AT brunomanadas effectofglobalatglknockoutonmurinefastingglucosekinetics AT arendheerschap effectofglobalatglknockoutonmurinefastingglucosekinetics AT johngjones effectofglobalatglknockoutonmurinefastingglucosekinetics |