Caveolins and Caveolae, Roles in Insulin Signalling and Diabetes

  • Peter Strålfors
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 729)

Abstract

Much data in the scientific literature demonstrate a fundamental involvement of caveolae in insulin action, although particular aspects remain matters of debate. The insulin receptor and part of the downstream signalling mediators are localized in or recruited to caveolae. Moreover, as part of the signalling, insulin receptors are rapidly endocytosed by caveolae in response to the hormone. The insulin regulated glucose transporter GLUT4 appears to localize to caveolae after insulin-stimulated translocation to the plasma membrane, while the endocytosis of GLUT4 may involve a clathrin-mediated process. Insulin resistance due to dysfunction of insulin signalling in target tissues is a primary cornerstone of Type 2 diabetes. Lack of caveolae makes animals and human beings insulin resistant, but there is presently no evidence that caveolae play a role in the pathogenesis of insulin resistance in obesity and Type 2 diabetes.

Keywords

Cholesterol Obesity Streptozotocin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Gustavsson J, Parpal S, Karlsson M et al. Localisation of the insulin receptor in caveolae of adipocyte plasma membrane. FASEB J 1999; 13:1961–1971.PubMedGoogle Scholar
  2. 2.
    Strålfors P. Insulin second messengers. BioEssays 1997; 19:327–335.PubMedGoogle Scholar
  3. 3.
    Karlsson M, Thorn H, Danielsson A et al. Colocalization of insulin receptor and insulin receptor substrate-1 to caveolae in primary human adipocytes. Cholesterol depletion blocks insulin signalling for metabolic and mitogenic control. Eur J Biochem 2004; 271:2471–2479.PubMedGoogle Scholar
  4. 4.
    Parpal S, Karlsson M, Thorn H et al. Cholesterol depletion disrupts caveolae and insulin receptor signaling for metabolic control via IRS-1, but not for MAP-kinase control. J Biol Chem 2001; 276:9670–9678.PubMedGoogle Scholar
  5. 5.
    Örtegren U, Yin L, Öst A et al. Separation and characterization of caveolae subclasses in the plasma membrane of primary adipocytes, segregation of specific proteins and functions. FEBS J 2006; 273:3381–3392.PubMedGoogle Scholar
  6. 6.
    Foti M, Porcheron G, Fournier M et al. The neck of caveolae is a distinct plasma membrane subdomain that concentrates insulin receptors in 3T3-L1 adipocytes. Proc Natl Acad Sci USA 2007; 104:1242–1247.PubMedGoogle Scholar
  7. 7.
    Kabayama K, Sato T, Saito K et al. Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance. Proc Natl Acad Sci USA 2007; 104:13678–13683.PubMedGoogle Scholar
  8. 8.
    Smith RM, Jarett L. Quantitative ultrastructural analysis of receptor-mediated insulin uptake into adipocytes. J Cell Physiol 1983; 115:199–207.PubMedGoogle Scholar
  9. 9.
    Goldberg RI, Smith RM, Jarett L. Insulin and alfa2-makroglobulin-methylamine undergo endocytosis by different mechanisms in rat adipocytes: I. Comparison of cell surface events. J Cell Physiol 1987; 133:203–212.PubMedGoogle Scholar
  10. 10.
    Carpentier J, Obberghen EV, Gorden P et al. Surface redistribution of 125I-insulin in cultured human lymphocytes. J Cell Biol 1981; 91:17–25.PubMedGoogle Scholar
  11. 11.
    Corley-Mastick C, Brady MJ, Saltiel AR. Insulin-stimulates the tyrosine phosphorylation of caveolin. J Cell Biol 1995; 129:1523–1531.Google Scholar
  12. 12.
    Souto RP, Vallega G, Wharton J et al. Immunopurification and characterization of rat adipocyte caveolae suggest their dissociation from insulin signaling. J Biol Chem 2003; 278:18321–18329.PubMedGoogle Scholar
  13. 13.
    Corley Mastick C, Brady MJ, Saltiel AR. Insulin stimulates the tyrosine phosphorylation of caveolin. J Cell Biol 1995; 129:1523–1531.Google Scholar
  14. 14.
    Thorn H, Stenkula KG, Karlsson M et al. Cell surface orifices of caveolae and localization of caveolin to the necks of caveolae in adipocytes. Mol Biol Cell 2003; 14:3967–3976.PubMedGoogle Scholar
  15. 15.
    Örtegren U, Karlsson M, Blazic N et al. Lipids and glycosphingolipids in caveolae and surrounding plasma membrane of primary rat adipocytes. Eur J Biochem 2004; 271:2028–2036.PubMedGoogle Scholar
  16. 16.
    Örtegren U, Aboulaich N, Öst A et al. A role for caveolae as metabolic platforms. Trends Endocrinol Metab 2007; 18:344–349.PubMedGoogle Scholar
  17. 17.
    Sin-Oh Y, Cho KA, Jin-Ryu S et al. Regulation of insulin response in skeletal muscle cells by caveolin status. J Cell Biochem 2006; 99:747–758.Google Scholar
  18. 18.
    Hahn-Obercyger M, Graeve L, Madar Z. A high-cholesterol diet increases the association between caveolae and insulin receptors in rat liver. J Lipid Res 2009; 50:98–107.PubMedGoogle Scholar
  19. 19.
    Balbis A, Baquiran G, Mournier C et al. Effect of insulin on caveolae-enriched membrane domains in rat liver. J Biol Chem 2004; 279:39348–39357.PubMedGoogle Scholar
  20. 20.
    Wang H, Liu Z, Li G et al. The vascular endothelial cell mediates insulin transport into skeletal muscle. Am J Physiol 2006; 291:E323–E332.Google Scholar
  21. 21.
    King GL, Johnson SM. Receptor-mediated transport of insulin across endothelial cells. Science 1985; 227:1583–1586.PubMedGoogle Scholar
  22. 22.
    Uhles S, Moede T, Leibiger B et al. Isoform-specific insulin receptor signaling involves different plasma membrane domains. J Cell Biol 2003; 163:1327–1337.PubMedGoogle Scholar
  23. 23.
    Otsu K, Toya Y, Oshikawa J et al. Caveolin gene transfer improves glucose metabolism in diabetic mice. Am J Physiol 2010; 298:C450–C456.Google Scholar
  24. 24.
    Fagerholm S, Örtegren U, Karlsson M et al. Rapid insulin-dependent endocytosis of the insulin receptor by caveolae in primary adipocytes. PLoS ONE 2009; 4:e5985.PubMedGoogle Scholar
  25. 25.
    Mineo C, Gill GN, Anderson RGW. Regulated migration of epidermal growth factor receptor from caveolae. J Biol Chem 1999; 274:30636–30643.PubMedGoogle Scholar
  26. 26.
    Vainio S, Heino S, Månsson J-E et al. Dynamic association of human insulin receptor with lipid rafts in cells lacking caveolae. EMBO Rep 2002; 3:95–100.PubMedGoogle Scholar
  27. 27.
    Brännmark C, Palmér R, Glad ST et al. Mass and information feedbacks through receptor endocytosis govern insulin signaling as revealed using a parameter-free modeling framework. J Biol Chem 2010; 285:20171–20179.PubMedGoogle Scholar
  28. 28.
    Cedersund G, Roll J, Ulfhielm E et al. Model-based hypothesis testing of key mechanisms in initial phase of insulin signaling. PLoS Comput Biol 2008; 4:e1000096.PubMedGoogle Scholar
  29. 29.
    Yamamoto M, Toya Y, Schwencke C et al. Caveolin is an activator of insulin receptor signaling. J Biol Chem 1998; 273:26962–26968.PubMedGoogle Scholar
  30. 30.
    Nystrom FH, Chen H, Cong L-N et al. Caveolin-1 interacts with the insulin receptor and can differentially modulate insulin signaling in transfected Cos-7 cells and rat adipose cells. Mol Endocrinol 1999; 13:2013–2024.PubMedGoogle Scholar
  31. 31.
    Strålfors P. Insulin signaling and caveolae. Adv Mol Cell Biol 2005; 36:141–169.Google Scholar
  32. 32.
    Yamashita THA, Haluzik M, Mizukami H et al. Enhanced insulin sensitivity in mice lacking ganglioside GM3. Proc Natl Acad Sci USA 2003; 100:3445–3449.PubMedGoogle Scholar
  33. 33.
    Stenkula KG, Thorn H, Frank N et al. Human, but not rat, IRS1 targets to the plasma membrane in both human and rat adipocytes. Biochem Biophys Res Commun 2007; 363:840–845.PubMedGoogle Scholar
  34. 34.
    Chen J, Capozza F, Wu A et al. Regulation of insulin receptor substrate-1 expression levels by caveolin-1. J Cell Physiol 2008; 217:281–289.PubMedGoogle Scholar
  35. 35.
    Capozza F, Combs TP, Cohen AW et al. Caveolin-3 knockout mice show incrased adiposity and whole body insulin resistance, with ligand induced insulin receptor instability in skeletal muscle. Am J Physiol 2005; 288:C1317–1331.Google Scholar
  36. 36.
    Cohen AW, Razani B, Wang XB et al. Caveolin-1 deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue. Am J Physiol 2003; 285:C222–235.Google Scholar
  37. 37.
    Gonzalez-Munoz E, Lopez-Iglesias C, Calvo M et al. Caveolin-1 loss of function accelerates glucose transporter-4 and insulin receptor degradation in 3T3-L1 adipocytes. Endocrinology 2009; 150:3493–3502.PubMedGoogle Scholar
  38. 38.
    Panetta D, Biedi C, Repetto S et al. IGF-1 regulates caveolin-1 and IRS1 interaction in caveolae. Biochem Biophys Res Commun 2004; 316:240–243.PubMedGoogle Scholar
  39. 39.
    Pike LJ, Casey L. Localization and turnover of phosphatidylinositol 4,5-bisphosphate in caveolin-enriched membrane domains. J Biol Chem 1996; 271:26453–26456.PubMedGoogle Scholar
  40. 40.
    Fujita A, Cheng J, Tauchi-Sato K et al. A distinct pool of phosphatidylinositol 4,5-bisphosphate in caveolae revealed by a nanoscale labeling technique. Proc Natl Acad Sci USA 2009; 106:9256–9261.PubMedGoogle Scholar
  41. 41.
    Smythe GM, Rando TA. Altered caveolin-3 expression disrupts PI(3) kinase signaling leading to death of cultured cells. Exp Cell Res 2006; 312:2816–2825.PubMedGoogle Scholar
  42. 42.
    Caselli A, Mazzinghi B, Camici G et al. Some protein tyrosine phosphatases target in part to lipid rafts and interact with caveolin-1. Biochem Biophys Res Commun 2002; 296:692–697.PubMedGoogle Scholar
  43. 43.
    Venugopal J, Hanashiro K, Yang Z-Z et al. Identification and modulation of a caveolae-dependent signal pathway that regulates plaminogen activator inhibitor-1 in insulin resistant adipocytes. Proc Natl Acad Sci USA 2004; 101:17120–17125.PubMedGoogle Scholar
  44. 44.
    Sanchez-Wandelmer J, Davalos A, Herrera E et al. Inhibition of cholesterol biosynthesis disrupts lipid raft/caveolae and affects insulin receptor activation in 3T3-L1 preadipocytes. Biochim Biophys Acta 2009; 1788:1731–1739.PubMedGoogle Scholar
  45. 45.
    Fecchi K, Volonte D, Hezel MP et al. Spatial and temporal regulation of GLUT4 translocation by flotillin-1 and caveolin-3 in skeletal muscle cells. FASEB J 2006; 20:705–707.PubMedGoogle Scholar
  46. 46.
    Cohen AW, Combs TP, Scherer PE et al. Role of caveolin and caveolae in insulin signaling and diabetes. Am J Physiol 2003; 285:E1151–E1160.Google Scholar
  47. 47.
    Razani B, Lisanti MP. Caveolin-deficient mice: insight into caveolar function and human disease. J Clin Inv 2001; 108:1553–1561.Google Scholar
  48. 48.
    Razani B, Combs TP, Wang XB et al. Caveolin-1 deficient mice are lean, resistant to diet-induced obesity and show hyper-triglyceridemia with adipocyte abnormalities. J Biol Chem 2002; 277:8635–8647.PubMedGoogle Scholar
  49. 49.
    Kim CA, Delepine M, Boutet E et al. Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy. J Clin Endocrinol Metab 2008; 93:1129–1134.PubMedGoogle Scholar
  50. 50.
    Strålfors P. Autolysis of isolated adipocytes by endogenously produced fatty acids. FEBS Lett 1990; 263:153–154.PubMedGoogle Scholar
  51. 51.
    Pohl J, Ring A, Stremmel W. Uptake of long-chain fatty acids in HepG2 cells involves caveolae: analysis of a novel pathway. J Lipid Res 2002; 43:1390–1399.PubMedGoogle Scholar
  52. 52.
    Öst A, Örtegren U, Gustavsson J et al. Triacylglycerol is synthesized in a specific subclass of caveolae in primary adipocytes. J Biol Chem 2005; 280:5–8.PubMedGoogle Scholar
  53. 53.
    Pohl J, Ring A, Ehehalt R et al. Long-chain fatty acid uptake into adipocytes depends on lipid raft function. Biochemistry 2004; 43:4179–4187.PubMedGoogle Scholar
  54. 54.
    Aboulaich N, Vainonen J, Strålfors P et al. Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes. Biochem J 2004; 383:237–248.PubMedGoogle Scholar
  55. 55.
    Hill M, Bastiani M, Lutterforst R et al. PTRF-Cavin, a conserved cytoplasmic protein required for caveolae formation and fucntion. Cell 2008; 132:113–124.PubMedGoogle Scholar
  56. 56.
    Liu L, Brown D, McKee M et al. Deletion of PTRF/Cavin causes global loss of caveolae, dylipidemia and glucose intolerance. Cell Metab 2008; 8:310–317.PubMedGoogle Scholar
  57. 57.
    Hayashi YK, Matsuda C, Ogawa M et al. Human PTRF mutations cause secondary deficiency of caveolin resulting in muscular dystrophy with generalized lipodystrophy. J Clin Inv 2009; 119:2623–2633.Google Scholar
  58. 58.
    Rajab A, Straub V, McCann LJ et al. Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-cavin mutations. PLoS Gen 2010; 6:e1000874.Google Scholar
  59. 59.
    Shastry S, Delgado MR, Dirik E et al. Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations. Am J Med Genet 2010; 152A:2245–2253.PubMedGoogle Scholar
  60. 60.
    Kozak LP, Newman S, Chao P-M et al. The early nutritional evironment of mice determines the capacity for adipose tissue expansion by modulating genes of caveolae structure. PLoS ONE 2010; 5:e11015.PubMedGoogle Scholar
  61. 61.
    Catalan V, Gomez-Ambrosi J, Rodriguez A et al. Expression of caveolin-1 in human adipose tissue is upregulated in obesity and obesity-associated type 2 diabetes mellitus and related to inflammation. Clinical Endocrinology 2008; 68:213–219.PubMedGoogle Scholar
  62. 62.
    Oshikawa J, Otsu K, Toya Y et al. Insulin resistance in skeletal muscles of caveolin-3-null mice. Proc Natl Acad Sci USA 2004; 101:12670–11275.PubMedGoogle Scholar
  63. 63.
    Bruno C, Sotgia F, Gazzerro E et al. Caveolinopathies, caveolin-3 deficiency GeneReviews 2007; http://www. ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cav.Google Scholar
  64. 64.
    Moller DE, Benecke H, Flier JS. Biological activities of naturally occuring human insulin receptor mutations. Evidence that metabolic effects of insulin can be mediated by a kinase-deficient insulin receptor mutant. J Biol Chem 1991; 266:10995–11001.Google Scholar
  65. 65.
    Moller DE, Yokota A, Ginsberg-Fellner F et al. Functional properties of a naturally occuring Trp1200-Ser1200 mutation of the insulin receptor. Mol Endocrinol 1990; 4:1183–1191.PubMedGoogle Scholar
  66. 66.
    Iwanishi M, Haruta T, Takata Y et al. A mutation (Trp1193-Leu1193) in the tyrosine kinase domain of the insulin receptor associated with type A syndrome of insulin resistance. Diabetologia 1993; 36:414–422.PubMedGoogle Scholar
  67. 67.
    Imamura T, Haruta T, Takata Y et al. Involvement of heat shock protein 90 in the degradation of mutant insulin receptors by the proteasome. J Biol Chem 1998; 273:11183–11188.PubMedGoogle Scholar
  68. 68.
    Imamura T, Takata Y, Sasaoka T et al. Two naturally occuring mutations in the kinase domain of the insulin receptor accelerate degradation of the insulin receptor and impair the kinase activity. J Biol Chem 1994; 269:31019–31027.PubMedGoogle Scholar
  69. 69.
    Sawa T, Imamura T, Haruta T et al. Hsp70 family molecular chaperones and mutant insulin receptor: differential binding specificities of BiP and Hsp70/Hsc70 determines accumulation or degradation of insulin receptor. Biochem Biophys Res Commun 1996; 218:449–453.PubMedGoogle Scholar
  70. 70.
    Backer JM, Kahn CR, White MF. Tyrosine phosphorylation of the insulin receptor during insulin-stimulated internalization in rat hepatoma cells. J Biol Chem 1989; 264:1694–1701.PubMedGoogle Scholar
  71. 71.
    Cushman SW, Wardzala LJ. Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. J Biol Chem 1980; 255:4758–4762.PubMedGoogle Scholar
  72. 72.
    Suzuki K, Kono T. Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site. Proc Natl Acad Sci USA 1980; 77:2542–2545.PubMedGoogle Scholar
  73. 73.
    Antonescu CN, Foti M, Sauvonnet N et al. Ready, set, internalize: mechanisms and regulation of GLUT4 endocytosis. Bioscience Reports 2009; 29:1–11.PubMedGoogle Scholar
  74. 74.
    Scherer PE, Lisanti MP, Baldini G et al. Induction of caveolin during adipogenesis and association of GLUT4 with caveolin-rich vesicles. J Cell Biol 1994; 127:1233–1243.PubMedGoogle Scholar
  75. 75.
    Gustavsson J, Parpal S, Strålfors P. Insulin-stimulated glucose uptake involves the transition of glucose transporters to a caveolae-rich fraction within the plasma membrane: implications for type II diabetes. Mol Med 1996; 2:367–372.PubMedGoogle Scholar
  76. 76.
    Karlsson M, Thorn H, Parpal S et al. Insulin induces translocation of glucose transporter GLUT4 to plasma membrane caveolae in adipocytes. FASEB J 2001; 16:249–251.PubMedGoogle Scholar
  77. 77.
    Ros-Baro A, Lopez-Iglesias C, Peiro S et al. Lipid rafts are required for GLUT4 internalization in adipose cells. Proc Natl Acad Sci USA 2001; 98:12050–12055.PubMedGoogle Scholar
  78. 78.
    Koneru S, Penumathsa SV, Tirunavukkarasu M et al. Redox regulation of ischemic preconditioning is mediated by the differential activation of caveolins and their association with eNOS and GLUT-4. Am J Physiol 2007; 292:H2060–H2072.Google Scholar
  79. 79.
    Penumathsa SV, Thirunavukkarasu M, Samuel SM et al. Niacin bound chromium treatment induces myocardial Glut-4 translocation and caveolar interaction via Akt, AMPK and eNOS phosphorylation in streptozotocin induced diabetic rats after ischemia-reperfusion injury. Biochim Biophys Acta 2009; 1792:39–48.PubMedGoogle Scholar
  80. 80.
    Guo L, Zhou D, Pryse KM et al. Fatty acid 2-hydroxylase mediates diffusional mobility of raft-associated lipids, GLUT4 level and lipogenesis in 3T3-L1 adipocytes. J Biol Chem 2010; 285:25438–25447.PubMedGoogle Scholar
  81. 81.
    Plough T, Deurs Bv, Ai H et al. Analysis of GLUT4 distribution in whole skeletal muscle fibers: identification of distinct storage compartments that are recruited by insulin and muscle contraction. J Cell Biol 1998; 142:1429–1446.Google Scholar
  82. 82.
    Parton RG, Way M, Zorzi N et al. Caveolin-3 associates with developing T-tubules during muscle differentiation. J Cell Biol 1997; 136:137–154.PubMedGoogle Scholar
  83. 83.
    Galbiati F, Engelman JA, Volonte D et al. Caveolin-3 null mice show a loss of caveolae, changes in the microdomain distribution of the dystrophin-glycoprotein complex and T-tubule abnormalites. J Biol Chem 2001; 276:21425–21433.PubMedGoogle Scholar
  84. 84.
    Lee E, Marcucci M, Daniell L et al. Amphyphysin 2 (Bin1) and T-tubule biogenesis in muscle. Science 2002; 297:1193–1196.PubMedGoogle Scholar
  85. 85.
    Song KS, Scherer PE, Tang Z et al. Expression of caveolin-3 in skeletal, cardiac and smooth muscle cells. Caveolin-3 is a component of the sarcolemma and cofractionates with dystrophin and dystrophin-associated glycoproteins. J Biol Chem 1996; 271:15160–15165.PubMedGoogle Scholar
  86. 86.
    Joost HG, Weber TM, Cushman SW. Qualitative and quantitative comparison of glucose transport activity and glucose transporter concentration in plasma membranes from basal and insulin-stimulated rat adipose cells Biochem J 1988; 249:155–161.PubMedGoogle Scholar
  87. 87.
    Smith RM, Charron MJ, Shah N et al. Immunoelectron microscopic demonstration of insulin-stimulated translocation of glucose transporters to the plasma membrane of isolated rat adipocytes and masking of the carboxy-terminal epitope of intracellular GLUT4 Proc Natl Acad Sci USA 1991; 88:6893–6897.PubMedGoogle Scholar
  88. 88.
    Satoh S, Nishimura H, Clark AE et al. Use of bismannose photolabel to elucidate insulin-regulated GLUT4 subcellular trafficking kinetics in rat adipose cells J Biol Chem 1993; 268:17820–17829.PubMedGoogle Scholar
  89. 89.
    Yuan T, Hong S, Yao Y et al. Glut-4 is translocated to both caveolae and noncaveolar lipid rafts, but is partially internalized through caveolae in insulin-stimulated adipocytes. Cell Research 2007; 17:772–782.PubMedGoogle Scholar
  90. 90.
    Stenkula KG, Lizunov VA, Cushman SW et al. Insulin controls the spatial distribution of GLUT4 on the cell surface through regulation of its postfusion dispersal. Cell Metab 2010; 12:250–259.PubMedGoogle Scholar
  91. 91.
    Slot JW, Geuze HJ, Gigengack S et al. Immuno-localization of the insulin regulatable glucose transporter in brown adipose tissue of the rat. J Cell Biol 1991; 113:123–135.PubMedGoogle Scholar
  92. 92.
    Robinson LJ, Pang S, Harris DS et al. Translocation of the glucose transporter (GLUT4) to the cell surface in permeabilized 3T3-L1 adipocytes: effects of ATP, insulin and GTPγS and localization of GLUT4 to clathrin lattices. J Cell Biol 1992; 117:1181–1196.PubMedGoogle Scholar
  93. 93.
    Voldstedlund M, Tranum-Jensen J, Vinten J. Quantification of Na+/K+-ATPase and glucose transporter isoforms in rat adipocyte plasma membrane by immunogold labeling. J Membr Biol 1993; 136:63–73.PubMedGoogle Scholar
  94. 94.
    Malide D, Ramm G, Cushman SW et al. Immunoelectron microscopic evidence that GLUT4 translocation explains the stimulation of glucose transport in isolated rat white adipose cells. J Cell Sci 2000; 113:4203–4210.PubMedGoogle Scholar
  95. 95.
    Shigematsu S, Watson RT, Khan AH et al. The adipocyte plasma membrane caveolin functional/structural organization is necessary for the efficient endocytosis of GLUT4. J Biol Chem 2003; 278:10683–10690.PubMedGoogle Scholar
  96. 96.
    Tagawa A, Mezzacasa A, Hayer A et al. Assembly and trafficking of caveolar domains in the cell: caveolae as stable, cargo-triggered vesicular transporters. J Cell Biol 2005; 170:769–779.PubMedGoogle Scholar
  97. 97.
    Danielsson A, Öst A, Lystedt E et al. Insulin resistance in human adipocytes downstream of IRS1 after surgical cell isolation, but at the level of phosphorylation of IRS1 in type 2 diabetes. FEBS J 2005; 272:141–151.PubMedGoogle Scholar
  98. 98.
    Lizunov VA, Matsumoto H, Zimmerberg J et al. Insulin stimulates the halting, tethering and fusion of mobile GLUT4 vesicles in rat adipose cells. J Cell Biol 2005; 169:481–489.PubMedGoogle Scholar
  99. 99.
    Blot V, McGraw TE. GLUT4 is internalized by a cholesterol-dependent nystatin-sensitive mechanism inhibited by insulin. EMBO J 2006; 25:5648–5658.PubMedGoogle Scholar
  100. 100.
    Kandror KV, Stephens JM, Pilch PF. Expression and compartmentalization of caveolin in adipose cells: coordinate regulation with and structural segregation from GLUT4. J Cell Biol 1995; 129:999–1006.PubMedGoogle Scholar
  101. 101.
    Munoz P, Mora S, Sevilla L et al. Expression and insulin-regulated distribution of caveolin in skeletal muscle. Caveolin does not colocalize with GLUT4 in intracellular membranes J Biol Chem 1996; 271:8133–8139.PubMedGoogle Scholar
  102. 102.
    Nishimura H, Zarnowski MJ, Simpson IA. Glucose transporter recycling in rat adipose cells. Effects of potassium depletion. J Biol Chem 1993; 268:19246–19253.PubMedGoogle Scholar
  103. 103.
    Huang S, Lifshitz LM, Jones C et al. Insulin stimulates membrane fusion and GLUT4 accumulation in clathrin coats on adipocyte plasma membranes. Mol Cell Biol 2007; 27:3456–3469.PubMedGoogle Scholar
  104. 104.
    Antonescu CN, Diaz M, Femia G et al. Clathrin-dependent and independent endocytosis of glucose transporter 4 (GLUT4) in myoblasts: regulation by mitochondrial uncoupling. Traffic 2008; 9:1173–1190.PubMedGoogle Scholar
  105. 105.
    Thomsen P, Roepstorff K, Stahlhut M et al. Caveolae are highly immobile plasma membrane microdomains, which are not involved in constitutive endocytic trafficking. Mol Biol Cell 2002; 13:238–250.PubMedGoogle Scholar
  106. 106.
    Hommelgaard AM, Roepstorff K, Vilhardt F et al. Caveolae: Stable membrane domains with a potential for internalization. Traffic 2005; 6:720–724.PubMedGoogle Scholar
  107. 107.
    Pelkmans L, Kartenbeck J, Helenius A. Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-pathway to the ER. Nature Cell Biol 2001; 3:473–483.PubMedGoogle Scholar
  108. 108.
    Cheng Z-J, Singh RD, Marks DL et al. Membrane microdomains, caveolae and caveolar endocytosis of sphingolipids. Mol Membr Biol 2006; 23:101–110.PubMedGoogle Scholar
  109. 109.
    Danielsson A, Fagerholm S, Öst A et al. Short-term over-eating induces insulin resistance in fat cells in lean human subjects. Mol Med 2009; 15:228–234.PubMedGoogle Scholar
  110. 110.
    Björnholm M, Kawano Y, Lehtihet M et al. Insulin receptor substrate-1 phosphorylation and phosphatidylinositol 3-kinase acitivity in skeletal muscle from NIDDM subjects after in vivo insulin stimulation. Diabetes 1997; 46:524–527.PubMedGoogle Scholar
  111. 111.
    Danielsson A, Öst A, Nystrom FH et al. Attenuation of insulin-stimulated insulin receptor substrate-1 serine 307 phosphorylation in insulin resistance of type 2 diabetes. J Biol Chem 2005; 280:34389–34392.PubMedGoogle Scholar
  112. 112.
    Öst A, Danielsson A, Liden M et al. Retinol-binding protein-4 attenuates insulin-induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes. FASEB J 2007; 21:3696–3704.PubMedGoogle Scholar
  113. 113.
    Öst A, Svensson K, Ruishalme I et al. Attenuated mTOR signaling and enhanced autophagy in adipocytes from obese patients with type 2 diabetes. Mol Med 2010; 16:235–246.PubMedGoogle Scholar
  114. 114.
    Oh YS, Lee TS, Cheon GJ et al. Modulation of insulin sensitivity and caveolin-1 expression by orchidectomy in a non-obese type 2 diabetes model. Mol Med 2010; 16.Google Scholar
  115. 115.
    Tabit CE, Chung WB, Hamburg NM et al. Endothelial dysfunction in diabetes mellitus:molecular mechanisms and clinical implications. Rev Endocr Metab Dis 2010; 11:61–74.Google Scholar
  116. 116.
    Bergman RN. Editorial: Insulin action and distribution of tissue blod flow. J Clin Endocrinol Metab 2003; 88:4556–4558.PubMedGoogle Scholar
  117. 117.
    Schnitzer JE, Oh P, Pinney E et al. Filipin-sensitive caveolae-mediated transport in endothelium: reduced transcytosis, scavenger endocytosis and capillary permeability of select macromolecules. J Cell Biol 1994; 127:1217–1232.PubMedGoogle Scholar
  118. 118.
    Wang H, Wang AX, Liu Z et al. Insulin signaling stimulates insulin transport by bovine aortic endothelial cells. Diabetes 2008; 57:540–547.PubMedGoogle Scholar
  119. 119.
    Vicent D, Ilany J, Kondo T et al. The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance. J Clin Inv 2003; 111:1373–1380.Google Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Peter Strålfors
    • 1
  1. 1.Department of Clinical and Experimental MedicineUniversity of LinköpingLinköpingSweden

Personalised recommendations