CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice
CD36 (fatty acid translocase) is involved in high-affinity peripheral fatty acid uptake. Mice lacking CD36 exhibit increased plasma free fatty acid and triglyceride (TG) levels and decreased glucose levels. Studies in spontaneous hypertensive rats lacking functional CD36 link CD36 to the insulin-res...
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Format: | Article |
Language: | English |
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Elsevier
2003-12-01
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Series: | Journal of Lipid Research |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520319441 |
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doaj-2150088983384823a62a5b2f1b5ff95a |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jeltje R. Goudriaan Vivian E.H. Dahlmans Bas Teusink D. Margriet Ouwens Maria Febbraio J. Anton Maassen Johannes A. Romijn Louis M. Havekes Peter J. Voshol |
spellingShingle |
Jeltje R. Goudriaan Vivian E.H. Dahlmans Bas Teusink D. Margriet Ouwens Maria Febbraio J. Anton Maassen Johannes A. Romijn Louis M. Havekes Peter J. Voshol CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice Journal of Lipid Research fatty acid transport glucose metabolism hepatic steatosis hyperinsulinemic clamp |
author_facet |
Jeltje R. Goudriaan Vivian E.H. Dahlmans Bas Teusink D. Margriet Ouwens Maria Febbraio J. Anton Maassen Johannes A. Romijn Louis M. Havekes Peter J. Voshol |
author_sort |
Jeltje R. Goudriaan |
title |
CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice |
title_short |
CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice |
title_full |
CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice |
title_fullStr |
CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice |
title_full_unstemmed |
CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice |
title_sort |
cd36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2003-12-01 |
description |
CD36 (fatty acid translocase) is involved in high-affinity peripheral fatty acid uptake. Mice lacking CD36 exhibit increased plasma free fatty acid and triglyceride (TG) levels and decreased glucose levels. Studies in spontaneous hypertensive rats lacking functional CD36 link CD36 to the insulin-resistance syndrome. To clarify the relationship between CD36 and insulin sensitivity in more detail, we determined insulin-mediated whole-body and tissue-specific glucose uptake in CD36-deficient (CD36−/−) mice. Insulin-mediated whole-body and tissue-specific glucose uptake was measured by d-[3H]glucose and 2-deoxy-d-[1-3H]glucose during hyperinsulinemic clamp in CD36−/− and wild-type control littermates (CD36+/+) mice. Whole-body and muscle-specific insulin-mediated glucose uptake was significantly higher in CD36−/− compared with CD36+/+ mice. In contrast, insulin completely failed to suppress endogenous glucose production in CD36−/− mice compared with a 40% reduction in CD36+/+ mice. This insulin-resistant state of the liver was associated with increased hepatic TG content in CD36−/− mice compared with CD36+/+ mice (110.9 ± 12.0 and 68.9 ± 13.6 μg TG/mg protein, respectively). Moreover, hepatic activation of protein kinase B by insulin, measured by Western blot, was reduced by 54%.Our results show a dissociation between increased muscle and decreased liver insulin sensitivity in CD36−/− mice. |
topic |
fatty acid transport glucose metabolism hepatic steatosis hyperinsulinemic clamp |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520319441 |
work_keys_str_mv |
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doaj-2150088983384823a62a5b2f1b5ff95a2021-04-27T04:41:24ZengElsevierJournal of Lipid Research0022-22752003-12-01441222702277CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in miceJeltje R. Goudriaan0Vivian E.H. Dahlmans1Bas Teusink2D. Margriet Ouwens3Maria Febbraio4J. Anton Maassen5Johannes A. Romijn6Louis M. Havekes7Peter J. Voshol8TNO Prevention and Health, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Division of Haematology/Oncology, Cornell University, New York, NY 14850; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Diabetes, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology and General Internal Medicine, Leiden University Medical Center, Leiden, The NetherlandsTNO Prevention and Health, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Division of Haematology/Oncology, Cornell University, New York, NY 14850; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Diabetes, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology and General Internal Medicine, Leiden University Medical Center, Leiden, The NetherlandsTNO Prevention and Health, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Division of Haematology/Oncology, Cornell University, New York, NY 14850; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Diabetes, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology and General Internal Medicine, Leiden University Medical Center, Leiden, The NetherlandsTNO Prevention and Health, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Division of Haematology/Oncology, Cornell University, New York, NY 14850; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Diabetes, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology and General Internal Medicine, Leiden University Medical Center, Leiden, The NetherlandsTNO Prevention and Health, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Division of Haematology/Oncology, Cornell University, New York, NY 14850; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Diabetes, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology and General Internal Medicine, Leiden University Medical Center, Leiden, The NetherlandsTNO Prevention and Health, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Division of Haematology/Oncology, Cornell University, New York, NY 14850; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Diabetes, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology and General Internal Medicine, Leiden University Medical Center, Leiden, The NetherlandsTNO Prevention and Health, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Division of Haematology/Oncology, Cornell University, New York, NY 14850; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Diabetes, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology and General Internal Medicine, Leiden University Medical Center, Leiden, The NetherlandsTNO Prevention and Health, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Division of Haematology/Oncology, Cornell University, New York, NY 14850; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Diabetes, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology and General Internal Medicine, Leiden University Medical Center, Leiden, The NetherlandsTNO Prevention and Health, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Division of Haematology/Oncology, Cornell University, New York, NY 14850; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Diabetes, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology and General Internal Medicine, Leiden University Medical Center, Leiden, The NetherlandsCD36 (fatty acid translocase) is involved in high-affinity peripheral fatty acid uptake. Mice lacking CD36 exhibit increased plasma free fatty acid and triglyceride (TG) levels and decreased glucose levels. Studies in spontaneous hypertensive rats lacking functional CD36 link CD36 to the insulin-resistance syndrome. To clarify the relationship between CD36 and insulin sensitivity in more detail, we determined insulin-mediated whole-body and tissue-specific glucose uptake in CD36-deficient (CD36−/−) mice. Insulin-mediated whole-body and tissue-specific glucose uptake was measured by d-[3H]glucose and 2-deoxy-d-[1-3H]glucose during hyperinsulinemic clamp in CD36−/− and wild-type control littermates (CD36+/+) mice. Whole-body and muscle-specific insulin-mediated glucose uptake was significantly higher in CD36−/− compared with CD36+/+ mice. In contrast, insulin completely failed to suppress endogenous glucose production in CD36−/− mice compared with a 40% reduction in CD36+/+ mice. This insulin-resistant state of the liver was associated with increased hepatic TG content in CD36−/− mice compared with CD36+/+ mice (110.9 ± 12.0 and 68.9 ± 13.6 μg TG/mg protein, respectively). Moreover, hepatic activation of protein kinase B by insulin, measured by Western blot, was reduced by 54%.Our results show a dissociation between increased muscle and decreased liver insulin sensitivity in CD36−/− mice.http://www.sciencedirect.com/science/article/pii/S0022227520319441fatty acid transportglucose metabolismhepatic steatosishyperinsulinemic clamp |