CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice - PubMed (original) (raw)

. 2003 Dec;44(12):2270-7.

doi: 10.1194/jlr.M300143-JLR200. Epub 2003 Aug 16.

Affiliations

• PMID: 12923231
• DOI: 10.1194/jlr.M300143-JLR200

Free article

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

Jeltje R Goudriaan et al. J Lipid Res. 2003 Dec.

Free article

Abstract

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 microg 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.

PubMed Disclaimer

Similar articles

• Sixteen hours of fasting differentially affects hepatic and muscle insulin sensitivity in mice.
  Heijboer AC, Donga E, Voshol PJ, Dang ZC, Havekes LM, Romijn JA, Corssmit EP. Heijboer AC, et al. J Lipid Res. 2005 Mar;46(3):582-8. doi: 10.1194/jlr.M400440-JLR200. Epub 2004 Dec 1. J Lipid Res. 2005. PMID: 15576835
• Muscle-specific overexpression of CD36 reverses the insulin resistance and diabetes of MKR mice.
  Héron-Milhavet L, Haluzik M, Yakar S, Gavrilova O, Pack S, Jou WC, Ibrahimi A, Kim H, Hunt D, Yau D, Asghar Z, Joseph J, Wheeler MB, Abumrad NA, LeRoith D. Héron-Milhavet L, et al. Endocrinology. 2004 Oct;145(10):4667-76. doi: 10.1210/en.2003-1543. Epub 2004 Jul 1. Endocrinology. 2004. PMID: 15231693
• Adipose and muscle tissue profile of CD36 transcripts in obese subjects highlights the role of CD36 in fatty acid homeostasis and insulin resistance.
  Pietka TA, Schappe T, Conte C, Fabbrini E, Patterson BW, Klein S, Abumrad NA, Love-Gregory L. Pietka TA, et al. Diabetes Care. 2014 Jul;37(7):1990-7. doi: 10.2337/dc13-2835. Epub 2014 May 1. Diabetes Care. 2014. PMID: 24784828 Free PMC article.
• Rosiglitazone improves muscle insulin sensitivity, irrespective of increased triglyceride content, in ob/ob mice.
  Muurling M, Mensink RP, Pijl H, Romijn JA, Havekes LM, Voshol PJ. Muurling M, et al. Metabolism. 2003 Aug;52(8):1078-83. doi: 10.1016/s0026-0495(03)00109-4. Metabolism. 2003. PMID: 12898477
• The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications-Update in Pathogenesis, Treatment and Monitoring.
  Puchałowicz K, Rać ME. Puchałowicz K, et al. Cells. 2020 Aug 11;9(8):1877. doi: 10.3390/cells9081877. Cells. 2020. PMID: 32796572 Free PMC article. Review.

Cited by

• Peroxisome proliferator-activated receptor-γ in capillary endothelia promotes fatty acid uptake by heart during long-term fasting.
  Goto K, Iso T, Hanaoka H, Yamaguchi A, Suga T, Hattori A, Irie Y, Shinagawa Y, Matsui H, Syamsunarno MR, Matsui M, Haque A, Arai M, Kunimoto F, Yokoyama T, Endo K, Gonzalez FJ, Kurabayashi M. Goto K, et al. J Am Heart Assoc. 2013 Jan 18;2(1):e004861. doi: 10.1161/JAHA.112.004861. J Am Heart Assoc. 2013. PMID: 23525438 Free PMC article.
• G-protein-coupled bile acid receptor plays a key role in bile acid metabolism and fasting-induced hepatic steatosis in mice.
  Donepudi AC, Boehme S, Li F, Chiang JY. Donepudi AC, et al. Hepatology. 2017 Mar;65(3):813-827. doi: 10.1002/hep.28707. Epub 2016 Jul 30. Hepatology. 2017. PMID: 27351453 Free PMC article.
• Pharmacological treatment with FGF21 strongly improves plasma cholesterol metabolism to reduce atherosclerosis.
  Liu C, Schönke M, Zhou E, Li Z, Kooijman S, Boon MR, Larsson M, Wallenius K, Dekker N, Barlind L, Peng XR, Wang Y, Rensen PCN. Liu C, et al. Cardiovasc Res. 2022 Jan 29;118(2):489-502. doi: 10.1093/cvr/cvab076. Cardiovasc Res. 2022. PMID: 33693480 Free PMC article.
• Endothelial EphB4 maintains vascular integrity and transport function in adult heart.
  Luxán G, Stewen J, Díaz N, Kato K, Maney SK, Aravamudhan A, Berkenfeld F, Nagelmann N, Drexler HC, Zeuschner D, Faber C, Schillers H, Hermann S, Wiseman J, Vaquerizas JM, Pitulescu ME, Adams RH. Luxán G, et al. Elife. 2019 Nov 29;8:e45863. doi: 10.7554/eLife.45863. Elife. 2019. PMID: 31782728 Free PMC article.
• Targeting macrophage scavenger receptor 1 promotes insulin resistance in obese male mice.
  Cavallari JF, Anhê FF, Foley KP, Denou E, Chan RW, Bowdish DME, Schertzer JD. Cavallari JF, et al. Physiol Rep. 2018 Nov;6(22):e13930. doi: 10.14814/phy2.13930. Physiol Rep. 2018. PMID: 30485705 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Miscellaneous

  • NCI CPTAC Assay Portal