HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M300143-JLR200v1 44/12/2270    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goudriaan, J. R. Articles by Voshol, P. J. Search for Related Content PubMed PubMed Citation Articles by Goudriaan, J. R. Articles by Voshol, P. J. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 44, 2270-2277, December 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice

Jeltje R. Goudriaan^*, Vivian E. H. Dahlmans^*, Bas Teusink^*, D. Margriet Ouwens, Maria Febbraio, J. Anton Maassen, Johannes A. Romijn^**, Louis M. Havekes^*, and Peter J. Voshol^1,*,**

^* TNO 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 Netherlands

¹ To whom correspondence should be addressed. e-mail: pj.voshol{at}pg.tno.nl

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.

Abbreviations: CD36^-/-, CD36-deficient; CD36^+/+, wild-type control littermates; 2-DG, 2-deoxy-D-[1-³H]glucose; FFA, free fatty acid; SHR, spontaneous hypertensive rat; TG, triglyceride; VLDLr, VLDL receptor

Supplementary key words fatty acid transport • glucose metabolism • hepatic steatosis • hyperinsulinemic clamp

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. F. C. Glatz, J. J. F. P. Luiken, and A. Bonen Membrane Fatty Acid Transporters as Regulators of Lipid Metabolism: Implications for Metabolic Disease Physiol Rev, January 1, 2010; 90(1): 367 - 417. [Abstract] [Full Text] [PDF]

				R. L. Silverstein and M. Febbraio CD36, a Scavenger Receptor Involved in Immunity, Metabolism, Angiogenesis, and Behavior Sci. Signal., May 26, 2009; 2(72): re3 - re3. [Abstract] [Full Text] [PDF]

				A. Bonen, X.-X. Han, N. N. Tandon, J. F. C. Glatz, J. Lally, L. A. Snook, and J. J. F. P. Luiken FAT/CD36 expression is not ablated in spontaneously hypertensive rats J. Lipid Res., April 1, 2009; 50(4): 740 - 748. [Abstract] [Full Text] [PDF]

				V. Luangrath, M. R. Brodeur, D. Rhainds, and L. Brissette Mouse CD36 Has Opposite Effects on LDL and Oxidized LDL Metabolism In Vivo Arterioscler Thromb Vasc Biol, July 1, 2008; 28(7): 1290 - 1295. [Abstract] [Full Text] [PDF]

				L. Love-Gregory, R. Sherva, L. Sun, J. Wasson, T. Schappe, A. Doria, D.C. Rao, S. C. Hunt, S. Klein, R. J. Neuman, et al. Variants in the CD36 gene associate with the metabolic syndrome and high-density lipoprotein cholesterol Hum. Mol. Genet., June 1, 2008; 17(11): 1695 - 1704. [Abstract] [Full Text] [PDF]

				M. S. Desai, M. M. Mariscalco, A. Tawil, J. G. Vallejo, and C. W. Smith Atherogenic diet-induced hepatitis is partially dependent on murine TLR4 J. Leukoc. Biol., June 1, 2008; 83(6): 1336 - 1344. [Abstract] [Full Text] [PDF]

				E. T. Parlevliet, A. C. Heijboer, J. P. Schroder-van der Elst, L. M. Havekes, J. A. Romijn, H. Pijl, and E. P. M. Corssmit Oxyntomodulin ameliorates glucose intolerance in mice fed a high-fat diet Am J Physiol Endocrinol Metab, January 1, 2008; 294(1): E142 - E147. [Abstract] [Full Text] [PDF]

				D. P.Y. Koonen, R. L. Jacobs, M. Febbraio, M. E. Young, C.-L. M. Soltys, H. Ong, D. E. Vance, and J. R.B. Dyck Increased Hepatic CD36 Expression Contributes to Dyslipidemia Associated With Diet-Induced Obesity Diabetes, December 1, 2007; 56(12): 2863 - 2871. [Abstract] [Full Text] [PDF]

				T. Hajri, A. M. Hall, D. R. Jensen, T. A. Pietka, V. A. Drover, H. Tao, R. Eckel, and N. A. Abumrad CD36-Facilitated Fatty Acid Uptake Inhibits Leptin Production and Signaling in Adipose Tissue Diabetes, July 1, 2007; 56(7): 1872 - 1880. [Abstract] [Full Text] [PDF]

				A. Bonen, X.-X. Han, D. D. J. Habets, M. Febbraio, J. F. C. Glatz, and J. J. F. P. Luiken A null mutation in skeletal muscle FAT/CD36 reveals its essential role in insulin- and AICAR-stimulated fatty acid metabolism Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1740 - E1749. [Abstract] [Full Text] [PDF]

				C. A. Nagle, J. An, M. Shiota, T. P. Torres, G. W. Cline, Z.-X. Liu, S. Wang, R. L. Catlin, G. I. Shulman, C. B. Newgard, et al. Hepatic Overexpression of Glycerol-sn-3-phosphate Acyltransferase 1 in Rats Causes Insulin Resistance J. Biol. Chem., May 18, 2007; 282(20): 14807 - 14815. [Abstract] [Full Text] [PDF]

				M. Pravenec and T. W. Kurtz Molecular Genetics of Experimental Hypertension and the Metabolic Syndrome: From Gene Pathways to New Therapies Hypertension, May 1, 2007; 49(5): 941 - 952. [Abstract] [Full Text] [PDF]

				S. M. Clee and A. D. Attie The Genetic Landscape of Type 2 Diabetes in Mice Endocr. Rev., February 1, 2007; 28(1): 48 - 83. [Abstract] [Full Text] [PDF]

				A. M. van den Hoek, A. C. Heijboer, P. J. Voshol, L. M. Havekes, J. A. Romijn, E. P. M. Corssmit, and H. Pijl Chronic PYY3-36 treatment promotes fat oxidation and ameliorates insulin resistance in C57BL6 mice Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E238 - E245. [Abstract] [Full Text] [PDF]

				S. L. Gray, E. D. Nora, J. Grosse, M. Manieri, T. Stoeger, G. Medina-Gomez, K. Burling, S. Wattler, A. Russ, G. S.H. Yeo, et al. Leptin Deficiency Unmasks the Deleterious Effects of Impaired Peroxisome Proliferator-Activated Receptor {gamma} Function (P465L PPAR{gamma}) in Mice. Diabetes, October 1, 2006; 55(10): 2669 - 2677. [Abstract] [Full Text] [PDF]

				M. A. M. den Boer, P. J. Voshol, J. P. Schroder-van der Elst, E. Korsheninnikova, D. M. Ouwens, F. Kuipers, L. M. Havekes, and J. A. Romijn Endogenous Interleukin-10 Protects against Hepatic Steatosis but Does Not Improve Insulin Sensitivity during High-Fat Feeding in Mice Endocrinology, October 1, 2006; 147(10): 4553 - 4558. [Abstract] [Full Text] [PDF]

				N. D. Oakes, P. Thalen, E. Aasum, A. Edgley, T. Larsen, S. M. Furler, B. Ljung, and D. Severson Cardiac metabolism in mice: tracer method developments and in vivo application revealing profound metabolic inflexibility in diabetes Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E870 - E881. [Abstract] [Full Text] [PDF]

				C. R. Benton, X.-X. Han, M. Febbraio, T. E. Graham, and A. Bonen Inverse relationship between PGC-1{alpha} protein expression and triacylglycerol accumulation in rodent skeletal muscle J Appl Physiol, February 1, 2006; 100(2): 377 - 383. [Abstract] [Full Text] [PDF]

				J. R. Goudriaan, M. A. M. den Boer, P. C. N. Rensen, M. Febbraio, F. Kuipers, J. A. Romijn, L. M. Havekes, and P. J. Voshol CD36 deficiency in mice impairs lipoprotein lipase-mediated triglyceride clearance J. Lipid Res., October 1, 2005; 46(10): 2175 - 2181. [Abstract] [Full Text] [PDF]

				A. Grefhorst, J. Hoekstra, T. G. J. Derks, D. M. Ouwens, J. F. W. Baller, R. Havinga, L. M. Havekes, J. A. Romijn, and F. Kuipers Acute hepatic steatosis in mice by blocking {beta}-oxidation does not reduce insulin sensitivity of very-low-density lipoprotein production Am J Physiol Gastrointest Liver Physiol, September 1, 2005; 289(3): G592 - G598. [Abstract] [Full Text] [PDF]

				B. Franke-Fayard, C. J. Janse, M. Cunha-Rodrigues, J. Ramesar, P. Buscher, I. Que, C. Lowik, P. J. Voshol, M. A. M. den Boer, S. G. van Duinen, et al. From The Cover: Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration PNAS, August 9, 2005; 102(32): 11468 - 11473. [Abstract] [Full Text] [PDF]

				J. P. H. van Wijk, M. C. Cabezas, E. J. P. de Koning, T. J. Rabelink, R. van der Geest, and I. M. Hoepelman In Vivo Evidence of Impaired Peripheral Fatty Acid Trapping in Patients with Human Immunodeficiency Virus-Associated Lipodystrophy J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3575 - 3582. [Abstract] [Full Text] [PDF]

				A. C. Heijboer, E. Donga, P. J. Voshol, Z.-C. Dang, L. M. Havekes, J. A. Romijn, and E. P. M. Corssmit Sixteen hours of fasting differentially affects hepatic and muscle insulin sensitivity in mice J. Lipid Res., March 1, 2005; 46(3): 582 - 588. [Abstract] [Full Text] [PDF]

				X. Ma, S. Bacci, W. Mlynarski, L. Gottardo, T. Soccio, C. Menzaghi, E. Iori, R. A. Lager, A. R. Shroff, E. V. Gervino, et al. A common haplotype at the CD36 locus is associated with high free fatty acid levels and increased cardiovascular risk in Caucasians Hum. Mol. Genet., October 1, 2004; 13(19): 2197 - 2205. [Abstract] [Full Text] [PDF]

				A. M. van den Hoek, P. J. Voshol, B. N. Karnekamp, R. M. Buijs, J. A. Romijn, L. M. Havekes, and H. Pijl Intracerebroventricular Neuropeptide Y Infusion Precludes Inhibition of Glucose and VLDL Production by Insulin Diabetes, October 1, 2004; 53(10): 2529 - 2534. [Abstract] [Full Text] [PDF]

				A. M. van den Hoek, A. C. Heijboer, E. P.M. Corssmit, P. J. Voshol, J. A. Romijn, L. M. Havekes, and H. Pijl PYY3-36 Reinforces Insulin Action on Glucose Disposal in Mice Fed a High-Fat Diet Diabetes, August 1, 2004; 53(8): 1949 - 1952. [Abstract] [Full Text] [PDF]

				M. den Boer, P.J. Voshol, F. Kuipers, L.M. Havekes, and J.A. Romijn Hepatic Steatosis: A Mediator of the Metabolic Syndrome. Lessons From Animal Models Arterioscler Thromb Vasc Biol, April 1, 2004; 24(4): 644 - 649. [Abstract] [Full Text] [PDF]