Altered Substrate Utilization in the Diabetic Heart: Role of Lipoprotein Lipase

  • Thomas Chacko Pulinilkunnil
  • Nandakumar Sambandam
  • Brian Rodrigues
Part of the Progress in Experimental Cardiology book series (PREC, volume 9)


The heart has a limited potential to synthesize FFA and therefore FFA is supplied to cardiac cells from several sources: through lipolysis of endogenous cardiac triglyceride (TG) stores, or from exogenous sources in the blood. Lipoprotein lipase (LPL), a gate-keeping enzyme synthesized in cardiomyocytes, catalyzes the breakdown of the TG component of lipoproteins (very low density lipoproteins or VLDL, and chylomicrons) to provide FFA to the heart. It is the vascular endothelial-bound LPL that determines the rate of plasma TG clearance and hence, it is also called heparin-releasable “functional” LPL. Functional LPL is regulated by numerous dietary and hormonal factors, and is sensitive to pathophysiological alterations like those observed during diabetes. In this condition, lack of insulin impairs cardiac glucose transport and oxidation, resulting in FFA becoming the preferred means of energy supply. To make available this increased requirement of the heart for FFA, diabetic heart upregulates its luminal LPL activity. Chronically elevated cardiac LPL during diabetes can result in abnormal FFA supply and utilization by the heart tissue that could potentially initiate and sustain cardiac dysfunction during diabetes. As effective blood glucose control is difficult during Type 1 diabetes, it is conceivable that a parallel increase in functional cardiac LPL activity in insulin-treated diabetic individuals may predispose them to premature death from cardiac disease. By gaining more insight into the initial metabolic processes in the diabetic heart, we can attempt to piece together a part of the cascade of events leading to diabetic cardiomyopathy. Therefore understanding both the role and the mechanism(s) of dysregulation of cardiac LPL activity in the overall disease process could attenuate cardiovascular complications associated with diabetes.

Key words

Diabetes STZ LPL and FFA 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Regan TJ, Weisse AB. 1992. Diabetic cardiomyopathy. J Am Coll Cardiol 19:1165–1166.PubMedCrossRefGoogle Scholar
  2. 2.
    Rodrigues B, Xiang H, McNeill JH. 1988. Effect of L-carnitine treatment on lipid metabolism and cardiac performance in chronically diabetic rats. Diabetes 37:1358–1364.PubMedCrossRefGoogle Scholar
  3. 3.
    Rodrigues B, Cam MC, McNeill JH. 1995. Myocardial substrate metabolism: implications for diabetic cardiomyopathy. J Mol Cell Cardiol 27:169–179.PubMedCrossRefGoogle Scholar
  4. 4.
    van der Vusse GJ, Glatz JF, Stam HC, Reneman RS. 1992. Fatty acid homeostasis in the normoxic and ischemic heart. Physiol Rev 72:881–940.PubMedGoogle Scholar
  5. 5.
    Randle PJ, Hales CN, Garland PB, Newsholme EA. 1963. The glucose fatty acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785–789.PubMedCrossRefGoogle Scholar
  6. 6.
    Rodrigues B, McNeill JH. 1992. The diabetic heart: metabolic causes for the development of a cardiomyopathy. Cardiovasc Res 26:913–922.PubMedCrossRefGoogle Scholar
  7. 7.
    Eckel RH. 1989. Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases. N Engl J Med 320:1060–1068.PubMedCrossRefGoogle Scholar
  8. 8.
    O’Brien KD, Ferguson M, Gordon D, Deeb SS, Chait A. 1994. Lipoprotein lipase is produced by cardiac myocytes rather than interstitial cells in human myocardium. Arterioscler Thromb 14: 1445–1451.PubMedCrossRefGoogle Scholar
  9. 9.
    Hamosh M, Hamosh P. 1983. Lipoprotein lipase: its physiological and clinical significance. Mol Aspects Med 6:199–289.PubMedCrossRefGoogle Scholar
  10. 10.
    Rodrigues B, Braun JE, Spooner M, Severson DL. 1992. Regulation of lipoprotein lipase activity in cardiac myocytes from control and diabetic rat hearts by plasma lipids. Can J Physiol Pharmacol 70:1271–1279.PubMedCrossRefGoogle Scholar
  11. 11.
    Murthy VK, Bauman MD, Shipp JC. 1983. Regulation of triacylglycerol lipolysis in the perfused hearts of normal and diabetic rats. Diabetes 32:718–722.PubMedGoogle Scholar
  12. 12.
    Kenno KA, Severson DL. 1985. Lipolysis in isolated myocardial cells from diabetic rat hearts. Am J Physiol 249:H1024–H1030.PubMedGoogle Scholar
  13. 13.
    Chattopadhyay J, Thompson EW, Schmid HH. 1990. Elevated levels of nonesterified fatty acids in the myocardium of alloxan diabetic rats. Lipids 25:307–310.PubMedCrossRefGoogle Scholar
  14. 14.
    Elkeles RS, Hambley J. 1977. The effects of fasting and streptozotocin diabetes on hepatic triglyceride lipase activity in the rat. Diabetes 26:58–60.PubMedCrossRefGoogle Scholar
  15. 15.
    Veeraraghavan K, Murthy K, Bauman MD, Shipp J. 1983. Regulation of triacylglycerol lipolysis in the perfused hearts of normal and diabetic rats. Diabetes 32:718–722.Google Scholar
  16. 16.
    Inadera H, Tashiro J, Okubo Y, Ishikawa Y, Shirai K, Saito Y, Yoshida S. 1992. Response of lipoprotein lipase to calorie intake in streptozotocin-induced diabetic rats. Scand J Clin Lab Invest 52: 797–802.PubMedCrossRefGoogle Scholar
  17. 17.
    Rauramaa R, Kuusela P, Hietanen E. 1980. Adipose, muscle and lung tissue lipoprotein lipase activities in young streptozotocin treated rats. Horm Metab Res 12:591–595.PubMedCrossRefGoogle Scholar
  18. 18.
    Stam H, Schoonderwoerd K, Breeman W, Hulsmann WC. 1984. Effects of hormones, fasting and diabetes on triglyceride lipase activities in rat heart and liver. Horm Metab Res 16:293–297.PubMedCrossRefGoogle Scholar
  19. 19.
    Nomura T, Hagino Y, Gotoh M, Iguchi A, Sakamoto N. 1984. The effects of streptozotocin diabetes on tissue specific lipase activities in the rat. Lipids 19:594–599.PubMedCrossRefGoogle Scholar
  20. 20.
    Tavangar K, Murata Y, Pedersen ME, Goers JF, Hofffnan AR, Kraemer FB. 1992. Regulation of lipoprotein lipase in the diabetic rat. J Clin Invest 90:1672–1678.PubMedCrossRefGoogle Scholar
  21. 21.
    O’Looney P, Vander Maten M, Vahouny GV. 1983. Insulin-mediated modifications of myocardial lipoprotein lipase and lipoprotein metabolism. J Biol Chem 258:12994–13001.PubMedGoogle Scholar
  22. 22.
    Deshaies Y, Geloen A, Paulin A, Bukowiecki LJ. 1990. Restoration of lipoprotein lipase activity in insulin-deficient rats by insulin infusion is tissue specific. Can J Physiol Pharmacol 69:746–751.CrossRefGoogle Scholar
  23. 23.
    Braun JE, Severson DL. 1992. Regulation of the synthesis, processing and translocation of lipoprotein lipase. Biochem J 287:337–347.PubMedGoogle Scholar
  24. 24.
    Rodrigues B, Severson DL. 1993. Acute diabetes does not reduce heparin-releasable lipoprotein lipase activity in perfused hearts from Wistar-Kyoto rats. Can J Physiol Pharmacol 71:657–661.PubMedCrossRefGoogle Scholar
  25. 25.
    Liu L, Severson DL. 1995. Myocardial lipoprotein lipase activity: regulation by diabetes and fructose-induced hypertriglyceridemia. Can J Physiol Pharmacol 73:369–377.PubMedCrossRefGoogle Scholar
  26. 26.
    Previato L, Parrott CL, Santamarina-Fojo S, Brewer HB, Jr. 1991. Transcriptional regulation of the human lipoprotein lipase gene in 3T3-L1 adipocytes. J Biol Chem 266:18958–18963.PubMedGoogle Scholar
  27. 27.
    Ben-Zeev O, Doolittle MH, Davis RC, Elovson J, Schotz MC. 1992. Maturation of lipoprotein lipase. Expression of full catalytic activity requires glucose trimming but not translocation to the cis-Golgi compartment. J Biol Chem 267:6219–6227.PubMedGoogle Scholar
  28. 28.
    Vannier C, Ailhaud G. 1989. Biosynthesis of lipoprotein lipase in cultured mouse adipocytes. II. Processing, subunit assembly, and intracellular transport. J Biol Chem 264:13206–13216.PubMedGoogle Scholar
  29. 29.
    Liu G, Bengtsson-Olivecrona G, Olivecrona T. 1993. Assembly of lipoprotein lipase in perfused guinea-pig hearts. Biochem J 292:277–282.PubMedGoogle Scholar
  30. 30.
    Scow RO, Schultz CJ, Park JW, Blanchette-Mackie EJ. 1998. Combined lipase deficiency (cld/cld) in mice affects differently post-translational processing of lipoprotein lipase, hepatic lipase and pancreatic lipase. Chem Phys Lipids 93:149–155.PubMedCrossRefGoogle Scholar
  31. 31.
    Rothman JE, Wieland FT. 1996. Protein sorting by transport vesicles. Science 272:227–234.PubMedCrossRefGoogle Scholar
  32. 32.
    Olivevrona T, Olivecrona GB. 1993. Lipoprotein lipase and hepatic lipase. Curr Opin Lipidol 4:187.CrossRefGoogle Scholar
  33. 33.
    Stins MF, Maxfeild FR, Goldberg IJ. 1992. Polarized binding of lipoprotein lipase to endothelial cells: implications for its physiological actions. Arterioscler Thromb 12:1437–1446.PubMedCrossRefGoogle Scholar
  34. 34.
    Anderson LG, Carroll R, Ewart HS, Acharya A, Severson DL. 1997. Fatty acid reduce heparin releasable LPL activity in cultured cardiomyocytes from the rat heart. Am J Physiol 273:E759–E769.PubMedGoogle Scholar
  35. 35.
    Shaul TC, Freidman G, Olivecrona GB, Vlodavsky I, Shavit FB. 1990. Interaction of lipoprotein lipase with sub endothelial extracellular matrix. Biochem Biophys Acta 1042:168–175.CrossRefGoogle Scholar
  36. 36.
    Blanchette-Mackie EJ, Dwyer NK, Amende LA. 1989. Cytochemical studies of lipid metabolism: immunogold probes for lipoprotein lipase and cholesterol. Am J Anat 185:255–263.PubMedCrossRefGoogle Scholar
  37. 37.
    Saxena U, Klein MG, Goldberg IJ. 1991. Transport of lipoprotein lipase across endothelial cells. Proc Natl Acad Sci USA 88:2254–2258.PubMedCrossRefGoogle Scholar
  38. 38.
    Berryman DE, Bensadoun A. 1995. Heparan sulfate proteoglycans are primarily responsible for the maintenance of enzyme activity, binding, and degradation of lipoprotein lipase in Chinese hamster ovary cells. J Biol Chem 270:24525–24531.PubMedCrossRefGoogle Scholar
  39. 39.
    Sivaram P, Paka L, Sasak A, Vanni-Reyes T, Yin B, Parthasarathy N, Wagner W, Goldberg IJ. 1997. Endothelial cell heparanase modulation of lipoprotein lipase activity. Evidence that heparan sulfate oligosaccharide is an extracellular chaperone. J Biol Chem 272:15753–15759.CrossRefGoogle Scholar
  40. 40.
    Michel CC. 1998. Capillaries, caveolae, calcium and cyclic nucleotides: a new look at microvascular permeability. J Mol Cell Cardiol 30:2541–2546.PubMedCrossRefGoogle Scholar
  41. 41.
    Oh P, Mcintosh DP, Schnitzer JE. 1998. Dynamin at the neck of caveolae mediates their budding to form transport vesicles by GTP-driven fission from the plasma membrane of endothelium. J Cell Biol 141:101–114.PubMedCrossRefGoogle Scholar
  42. 42.
    Niles WD, Malik AB. 1999. Endocytosis and exocytosis events regulate vesicle traffic in endothelial cells. J Membr Biol 167:85–101.PubMedCrossRefGoogle Scholar
  43. 43.
    Chajek T, Stein O, Stein Y. 1975. Interference with the transport of heparin-releasable lipoprotein lipase in the perfused rat heart by colchicine and vinblastine. Biochim Biophys Acta 388:260–268.PubMedCrossRefGoogle Scholar
  44. 44.
    Lespine A, Chap H, Perret B. 1997. Impaired secretion of heart lipoprotein lipase in cyclophos-phamide-treated rabbit. Biochim Biophys Acta 1345:77–85.PubMedCrossRefGoogle Scholar
  45. 45.
    Ewart HS, Severson DL. 1999. Insulin and dexamethasone stimulation of cardiac lipoprotein lipase activity involves the actin-based cytoskeleton. Biochem J 340:485–490.PubMedCrossRefGoogle Scholar
  46. 46.
    Stein O, Stein Y, Schwartz SP, Reshef A, Chajek-Shaul T, Ben-Nairn M, Friedman G, Leitersdorf E. 1991. Expression of lipoprotein lipase mRNA in rat heart is localized mainly to mesenchymal cells as studied by in situ hybridization. Arterioscler Thromb 11:857–863.PubMedCrossRefGoogle Scholar
  47. 47.
    Pedersen ME, Schotz MC. 1980. Rapid changes in rat heart lipoprotein lipase activity after feeding carbohydrate. J Nutr 110:481–487.PubMedGoogle Scholar
  48. 48.
    Camps L, Reina M, Llobera M, Vilaro S, Olivecrona T. 1990. Lipoprotein lipase: cellular origin and functional distribution. Am J Physiol 258:C673–C681.PubMedGoogle Scholar
  49. 49.
    Liu G, Olivecrona T. 1992. Synthesis and transport of lipoprotein lipase in perfused guinea pig hearts. Am J Physiol 263:H438–H446.PubMedGoogle Scholar
  50. 50.
    Liu GQ, OlivecronaT. 1991. Pulse-chase study on lipoprotein lipase in perfused guinea pig heart. Am J Physiol 261:H2044–H2050.PubMedGoogle Scholar
  51. 51.
    Rodrigues B, Cam MC, Jian K, Lim F, Sambandam N, Shepherd G. 1997. Differential effects of streptozotocin-induced diabetes on cardiac lipoprotein lipase activity. Diabetes 46:1346–1353.PubMedCrossRefGoogle Scholar
  52. 52.
    Currie RA, Eckel RH. 1992. Characterization of a high affinity octamer transcription factor binding site in the human lipoprotein lipase promoter. Arch Biochem Biophys 298:630–639.PubMedCrossRefGoogle Scholar
  53. 53.
    Enerback S, Gimble J. 1993. Lipoprotein lipase gene expression: physiological regulators at the transcriptional and post-transcriptional level. Biochim Biophys Acta 1169:107–125.PubMedCrossRefGoogle Scholar
  54. 54.
    Ranganathan G, Ong JM, Yukht A, Saghizadeh M, Simsolo KB, Pauer A, Kern PA. 1995. Tissue-specific expression of human lipoprotein lipase. Effect of the 3′-untranslated region on translation. J Biol Chem 270:7149–7155.PubMedCrossRefGoogle Scholar
  55. 55.
    Yukht A, Davis RC, Ong JM, Ranganathan G, Kern PA. 1995. Regulation of lipoprotein lipase translation by epinephrine in 3T3-L1 cells. Importance of the 3′ untranslated region. J Clin Invest 96:2438–2444.PubMedCrossRefGoogle Scholar
  56. 56.
    Mitchell JR, Jacobsson A, Kirchgessner TG, Schotz MC, Cannon B, Nedergaard J. 1992. Regulation of expression of the lipoprotein lipase gene in brown adipose tissue. Am J Physiol 263: E500–E506.PubMedGoogle Scholar
  57. 57.
    Ong JM, Kern PA. 1989. The role of glucose and glycosylation in the regulation of lipoprotein lipase synthesis and secretion in rat adipocytes. J Biol Chem 264:3177–3182.PubMedGoogle Scholar
  58. 58.
    Bergo M, Olivecrona G, Olivecrona T. 1996. Diurnal rhythms and effects of fasting and refeeding on rat adipose tissue lipoprotein lipase. Am J Physiol 271:E1092–E1097.PubMedGoogle Scholar
  59. 59.
    Klingenspor M, Ebbinghaus C, Hulshorst G, Stohr S, Spiegelhalter F, Haas K, Heldmaier G. 1996. Multiple regulatory steps are involved in the control of lipoprotein lipase activity in brown adipose tissue. J Lipid Res 37:1685–1695.PubMedGoogle Scholar
  60. 60.
    Masuno H, Okuda H. 1994. Role of processing of the oligosaccharide chains in the affinity of lipoprotein lipase for heparin. Biochim Biophys Acta 1212:125–128.PubMedCrossRefGoogle Scholar
  61. 61.
    Park JW, Oh MS, Yang JY, Park BH, Rho HW, Lim SN, Jhee EC, Kim HR. 1995. Glycosylation, dimerization, and heparin affinity of lipoprotein lipase in 3T3-L1 adipocytes. Biochim Biophys Acta 1254:45–50.PubMedCrossRefGoogle Scholar
  62. 62.
    Cheng CF, Oosta GM, Bensadoun A, Rosenberg RD. 1981. Binding of lipoprotein lipase to endothelial cells in culture. J Biol Chem 256:12893–12898.PubMedGoogle Scholar
  63. 63.
    Shimada K, Gill PJ, Silbert JE, Douglas WH, Fanburg BL. 1981. Involvement of cell surface heparin sulfate in the binding of lipoprotein lipase to cultured bovine endothelial cells. J Clin Invest 68:995–1002.PubMedCrossRefGoogle Scholar
  64. 64.
    Wang-Iverson P, Brown WV. 1982. Interaction of lipoprotein lipase with cultured endothelial cells. Ann NY Acad Sci 401:92–101.PubMedCrossRefGoogle Scholar
  65. 65.
    Williams MP, Streeter HB, Wusteman FS, Cryer A. 1983. Heparan sulphate and the binding of lipoprotein lipase to porcine thoracic aorta endothelium. Biochim Biophys Acta 756:83–91.PubMedCrossRefGoogle Scholar
  66. 66.
    Cisar LA, Hoogewerf AJ, Cupp M, Rapport CA, Bensadoun A. 1989. Secretion and degradation of lipoprotein lipase in cultured adipocytes. Binding of lipoprotein lipase to membrane heparan sulfate proteoglycans is necessary for degradation. J Biol Chem 264:1767–1774.PubMedGoogle Scholar
  67. 67.
    Chajek-Shaul T, Halimi O, Ben-Nairn M, Stein O, Stein Y 1989. Phosphatidylinositol-specific phospholipase C releases lipoprotein lipase from the heparin releasable pool in rat heart cell cultures. Biochim Biophys Acta 1014:178–183.PubMedCrossRefGoogle Scholar
  68. 68.
    Parthasarathy N, Goldberg IJ, Sivaram P, Mulloy B, Flory DM, Wagner WD. 1994. Oligosaccharide sequences of endothelial cell surface heparan sulfate proteoglycan with affinity for lipoprotein lipase. J Biol Chem 269:22391–22396.PubMedGoogle Scholar
  69. 69.
    Chevreuil O, Hultin M, Ostergaard P, Olivecrona T. 1993. Depletion of lipoprotein lipase after heparin administration. Arterioscler Thromb 13:1391–1396.PubMedCrossRefGoogle Scholar
  70. 70.
    de Man FH, de Beer F, van der Laarse A, Smelt AH, Havekes LM. 1997. Lipolysis of very low density lipoproteins by heparan sulfate proteoglycan-bound lipoprotein lipase. J Lipid Res 38: 2465–2472.PubMedGoogle Scholar
  71. 71.
    Eckel RH, Fujimoto WY, Brunzell JD. 1978. Insulin regulation of lipoprotein lipase in cultured 3T3-L1 cells. Biochem Biophys Res Commun 84:1069–1075.PubMedCrossRefGoogle Scholar
  72. 72.
    Spooner PM, Chernick SS, Garrison MM, Scow RO. 1979. Insulin regulation of lipoprotein lipase activity and release in 3T3-L1 adipocytes. Separation and dependence of hormonal effects on hexose metabolism and synthesis of RNA and protein. J Biol Chem 254:10021–10029.PubMedGoogle Scholar
  73. 73.
    Chan BL, Lisanti MP, Rodriguez-Boulan E, Saltiel AR. 1988. Insulin-stimulated release of lipoprotein lipase by metabolism of its phosphatidylinositol anchor. Science 241:1670–1672.PubMedCrossRefGoogle Scholar
  74. 74.
    Muller G, Dearey EA, Korndorfer A, Bandlow W. 1994. Stimulation of a glycosyl-phosphatidyli-nositol-specific phospholipase by insulin and the sulfonylurea, glimepiride, in rat adipocytes depends on increased glucose transport. J Cell Biol 126:1267–1276.PubMedCrossRefGoogle Scholar
  75. 75.
    Wolle J, Ferguson E, Devall LJ, Newton RS, Saxena U. 1995. Identification of a novel 85-kDa lipoprotein lipase binding protein on human aortic endothelial cell surface. Biochem Biophys Res Commun 216:906–912.PubMedCrossRefGoogle Scholar
  76. 76.
    Vilella E, Bengtsson-Olivecrona G, Stigbrand T, Jensen PE. 1994. Binding of lipoprotein lipase to alpha 2-macroglobulin. Biochem J 300:443–448.PubMedGoogle Scholar
  77. 77.
    Nielsen MS, Brejning J, Garcia R, Zhang H, Hayden MR, Vilaro S, Gliemann J. 1997. Segments in the C-terminal folding domain of lipoprotein lipase important for binding to the low density lipoprotein receptor-related protein and to heparan sulfate proteoglycans. J Biol Chem 272: 5821–5827.PubMedCrossRefGoogle Scholar
  78. 78.
    Lee JJ, Smith PJ, Fried SK. 1998. Mechanisms of decreased lipoprotein lipase activity in adipocytes of starved rats depend on duration of starvation. J Nutr 128:940–946.PubMedGoogle Scholar
  79. 79.
    Obunike JC, Sivaram P, Paka L, Low MG, Goldberg IJ. 1996. Lipoprotein lipase degradation by adipocytes: receptor-associated protein (PAP)-sensitive and proteoglycan-mediated pathways. J Lipid Res 37:2439–2449.PubMedGoogle Scholar
  80. 80.
    Hoogewerf AJ, Cisar LA, Evans DC, Bensadoun A. 1991. Effect of chlorate on the sulfation of lipoprotein lipase and heparan sulfate proteoglycans. Sulfation of heparan sulfate proteoglycans affects lipoprotein lipase degradation. J Biol Chem 266:16564–16571.PubMedGoogle Scholar
  81. 81.
    Sehayek E, Olivecrona T, Bengtsson-Olivecrona G, Vlodavsky I, Levkovitz H, Avner R, Eisenberg S. 1995. Binding to heparan sulfate is a major event during catabolism of lipoprotein lipase by HepG2 and other cell cultures. Atherosclerosis 114:1–8.PubMedCrossRefGoogle Scholar
  82. 82.
    Saxena U, Klein MG, Goldberg IJ. 1990. Metabolism of endothelial cell-bound lipoprotein lipase. Evidence for heparan sulfate proteoglycan-mediated internalization and recycling. J Biol Chem 265:12880–12886.PubMedGoogle Scholar
  83. 83.
    Bengtsson G, Olivecrona T. 1980. Lipoprotein lipase. Mechanism of product inhibition. Eur J Biochem 106:557–562.PubMedCrossRefGoogle Scholar
  84. 84.
    Saxena U, Goldberg IJ. 1990. Interaction of lipoprotein lipase with glycosaminoglycans and apolipoprotein C-II: effects of free-fatty-acids. Biochim Biophys Acta 1043:161–168.PubMedCrossRefGoogle Scholar
  85. 85.
    Robinson DS. 1960. The effect of changes in nutritional state on the lipolytic activity of rat adipose tissue. J Lipid Res 1:332–338.PubMedGoogle Scholar
  86. 86.
    Salaman MR, Robinson DS. 1966. Clearing-factor lipase in adipose tissue. A medium in which the enzyme activity of tissue from starved rats increases in vitro. Biochem J 99:640–647.PubMedGoogle Scholar
  87. 87.
    Robinson DS, Jennings MA. 1965. Release of clearing factor lipase by the perfused rat heart. J Lipid Res 6:222–229.PubMedGoogle Scholar
  88. 88.
    Pedersen ME, Schotz MC. 1980. Rapid changes in rat heart lipoprotein lipase activity after feeding carbohydrate. J Nutr 110:481–487.PubMedGoogle Scholar
  89. 89.
    Bergo M, Olivecrona G, Olivecrona T 1996. Forms of lipoprotein lipase in rat tissues: in adipose tissue the proportion of inactive lipase increases on fasting. Biochem J 313:893–898.PubMedGoogle Scholar
  90. 90.
    Ong JM, Simsolo KB, Saghizadeh M, Pauer A, Kern PA. 1994. Expression of lipoprotein lipase in rat muscle: regulation by feeding and hypothyroidism. J Lipid Res 35:1542–1551.PubMedGoogle Scholar
  91. 91.
    Ladu MJ, Kapsas H, Palmer WK. 1991. Regulation of lipoprotein lipase in adipose and muscle tissues during fasting. Am J Physiol 260:R953–R959.PubMedGoogle Scholar
  92. 92.
    Olivecrona T, Bergo M, Hultin M, Olivecrona G. 1995. Nutritional regulation of lipoprotein lipase. Can J Cardiol 11 Suppl G:73G–78G.PubMedGoogle Scholar
  93. 93.
    Doolittle MH, Ben-Zeev O, Elovson J, Martin D, Kirchgessner TG. 1990. The response of lipoprotein lipase to feeding and fasting. Evidence for posttranslational regulation. J Biol Chem 265: 4570–4577.PubMedGoogle Scholar
  94. 94.
    Schwartz RS, Brunzell JD. 1981. Increase of adipose tissue lipoprotein lipase activity with weight loss. J Clin Invest 67:1425–1430.PubMedCrossRefGoogle Scholar
  95. 95.
    Eckel RH, Yost TJ. 1987. Weight reduction increases adipose tissue lipoprotein lipase responsiveness in obese women. J Clin Invest 80:992–997.PubMedCrossRefGoogle Scholar
  96. 96.
    O’Looney PA, Vahouny GA. 1987. Diabetes and lipoprotein lipase activity: Lipoprotein lipase, 229–246 USA: Evener Publishers.Google Scholar
  97. 97.
    Simsolo KB, Ong JM, Saffari B, Kern PA. 1992. Effect of improved diabetes control on the expression of lipoprotein lipase in human adipose tissue. J Lipid Res 33:89–95.PubMedGoogle Scholar
  98. 98.
    Eckel RH, Yost TJ, Jensen DR. 1995. Alterations in lipoprotein lipase in insulin resistance. Int J Obes Relat Metab Disord 19 Suppl 1:S16–S21.PubMedGoogle Scholar
  99. 99.
    Maheux P, Azhar S, Kern PA, Chen YD, Reuven GM. 1997. Relationship between insulin-mediated glucose disposal and regulation of plasma and adipose tissue lipoprotein lipase. Diabetologia 40:850–858.PubMedCrossRefGoogle Scholar
  100. 100.
    Boivin A, Montplaisir I, Deshaies Y. 1994. Postprandial modulation of lipoprotein lipase in rats with insulin resistance. Am J Physiol 267:E620–E627.PubMedGoogle Scholar
  101. 101.
    Yost TJ, Froyd KK, Jensen DR, Eckel RH. 1995. Change in skeletal muscle lipoprotein lipase activity in response to insulin/glucose in non-insulin-dependent diabetes mellitus. Metabolism 44:786–790.PubMedCrossRefGoogle Scholar
  102. 102.
    Kashiwazaki K, Hirano T, Yoshino G, Kurokawa M, Tajima H, Adachi M. 1998. Decreased release of lipoprotein lipase is associated with vascular endothelial damage in NIDDM patients with microalbuminuria. Diabetes Care 21:2016–2020.PubMedCrossRefGoogle Scholar
  103. 103.
    Hansen PM, Jensen T, Egeberg J, Lithell H, Kofoed-Enevoldsen A, Deckert T. 1997. Skeletal muscle lipoprotein-lipase activity in insulin-dependent diabetic patients with and without albuminuria. J Diabetes Complications 11:230–235.PubMedCrossRefGoogle Scholar
  104. 104.
    Kessler J. 1963. Effect of diabetes and insulin on the activity of myocardial and adipose tissue lipoprotein lipase of rats. J Clin Invest 42:362–367.PubMedCrossRefGoogle Scholar
  105. 105.
    Braun JE, Severson DL. 1991. Diabetes reduces heparin- and phospholipase C-releasable lipoprotein lipase from cardiomyocytes. Am J Physiol 260:E477–E485.PubMedGoogle Scholar
  106. 106.
    Rodrigues B, Spooner M, Severson DL. 1992. Free fatty acids do not release lipoprotein lipase from isolated cardiac myocytes or perfused hearts. Am J Physiol 262:E216–E223.PubMedGoogle Scholar
  107. 107.
    Ewart HS, Carroll R, Severson DL. 1997. Lipoprotein lipase activity in rat cardiomyocytes is stimulated by insulin and dexamethasone. Biochem J 327:439–442.PubMedGoogle Scholar
  108. 108.
    Liu L, Severson DL. 1994. Regulation of myocardial lipoprotein lipase activity by diabetes and thyroid hormones. Can J Physiol Pharmacol 72:1259–1264.PubMedCrossRefGoogle Scholar
  109. 109.
    Carroll R, Liu L, Severson DL. 1995. Post-transcriptional mechanisms are responsible for the reduction in lipoprotein lipase activity in cardiomyocytes from diabetic rat hearts. Biochem J 310:67–72.PubMedGoogle Scholar
  110. 110.
    Liu L, Severson DL. 1996. Endothelial binding sites for lipoprotein lipase are not diminished in perfused hearts from diabetic rats. Can J Physiol Pharmacol 74:1204–1209.PubMedCrossRefGoogle Scholar
  111. 111.
    Wilson DE, Zeikus R, Chan IF. 1987. Relationship of organ lipoprotein lipase activity and ketonuria to hypertriglyceridemia in starved and streptozocin-induced diabetic rats. Diabetes 36:485–490.PubMedCrossRefGoogle Scholar
  112. 112.
    Hirano T, Mamo JC, Takeuchi H, Nagano S, Takahashi T. 1991. Correlation of insulin deficiency and hypertriglyceridemia in diabetic rats. Diabetes Res Clin Pract 12:173–180.PubMedCrossRefGoogle Scholar
  113. 113.
    Mamo JC, Hirano T, Sainsbury A, Fitzgerald AK, Redgrave TG. 1992. Hypertriglyceridemia is exacerbated by slow lipolysis of triacylglycerol-rich lipoproteins in fed but not fasted streptozotocin diabetic rats. Biochim Biophys Acta 1128:132–138.PubMedCrossRefGoogle Scholar
  114. 114.
    Staprans I, Pan XM, Rapp JH, Feingold KR. 1992. Chylomicron and chylomicron remnant metabolism in STZ-induced diabetic rats. Diabetes 41:325–333.PubMedCrossRefGoogle Scholar
  115. 115.
    Duerden JM, Gibbons GF. 1993. Restoration in vitro of normal rates of very-low-density lipoprotein triacylglycerol and apoprotein B secretion in hepatocyte cultures from diabetic rats. Biochem J 294:167–171.PubMedGoogle Scholar
  116. 116.
    Garg A. 1994. Management of dyslipidemia in IDDM patients. Diabetes Care 17:224–234.PubMedCrossRefGoogle Scholar
  117. 117.
    Yoshino G, Hirano T, Kazumi T. 1996. Dyslipidemia in diabetes mellitus. Diabetes Res Clin Pract 33:1–14.PubMedCrossRefGoogle Scholar
  118. 118.
    Taskinen MR. 1987. Lipoprotein lipase in diabetes. Diabetes Metab Rev 3:551–570.PubMedCrossRefGoogle Scholar
  119. 119.
    Ebara T, Hirano T, Mamo JC, Sakamaki R, Furukawa S, Nagano S, Takahashi T. 1994. Hyperlipidemia in streptozocin-diabetic hamsters as a model for human insulin-deficient diabetes: comparison to streptozocin-diabetic rats. Metabolism 43:299–305.PubMedCrossRefGoogle Scholar
  120. 120.
    Bagdade JD, Porte D, Jr., Bierman EL. 1968. Acute insulin withdrawal and the regulation of plasma triglyceride removal in diabetic subjects. Diabetes 17:127–132.PubMedGoogle Scholar
  121. 121.
    Jeppesen J, Hollenbeck CB, Zhou MY, Coulston AM, Jones C, Chen YD, Reaven GM. 1995. Relation between insulin resistance, hyperinsulinemia, postheparin plasma lipoprotein lipase activity, and postprandial lipemia. Arterioscler Thromb Vase Biol 15:320–324.CrossRefGoogle Scholar
  122. 122.
    Zhang Q, Cavallero E, Hoffmann MM, Cavanna J, Kay A, Charles A, Braschi S, Marz W, Perlemuter L, Jacotot B, Galton DJ. 1997. Mutations at the lipoprotein lipase gene locus in subjects with diabetes mellitus, obesity and lipaemia. Clin Sci (Lond) 93:335–341.Google Scholar
  123. 123.
    Knudsen P, Murtomaki S, Antikainen M, Ehnholm S, Lahdenpera S, Ehnholm C, Taskinen MR. 1997. The Asn-291→Ser and Ser-477→Stop mutations of the lipoprotein lipase gene and their significance for lipid metabolism in patients with hypertriglyceridaemia. Eur J Clin Invest 27:928–935.PubMedCrossRefGoogle Scholar
  124. 124.
    Ahn YI, Ferrell RE, Hamman RF, Kamboh MI. 1993. Association of lipoprotein lipase gene variation with the physiological components of the insulin-resistance syndrome in the population of the San Luis Valley, Colorado. Diabetes Care 16:1502–1506.PubMedCrossRefGoogle Scholar
  125. 125.
    Wang XL, McCredie RM, Wilcken DE. 1996. Common DNA polymorphisms at the lipoprotein lipase gene. Association with severity of coronary artery disease and diabetes. Circulation 93:1339–1345.PubMedCrossRefGoogle Scholar
  126. 126.
    Julien P, Vohl MC, Gaudet D, Gagne C, Levesque G, Despres JP, Cadelis F, Brun LD, Nadeau A, Ven Murthy MR. 1997. Hyperinsulinemia and abdominal obesity affect the expression of hypertriglyceridemia in heterozygous familial lipoprotein lipase deficiency. Diabetes 46:2063–2068.PubMedCrossRefGoogle Scholar
  127. 127.
    Tsutsumi K, Inoue Y, Shima A, Murase T. 1995. Correction of hypertriglyceridemia with low high-density lipoprotein cholesterol by the novel compound NO-1886, a lipoprotein lipase-promoting agent, in STZ-induced diabetic rats. Diabetes 44:414–417.PubMedCrossRefGoogle Scholar
  128. 128.
    Groop PH, Elliott T, Ekstrand A, Franssila-Kallunki A, Friedman R, Viberti GC, Taskinen MR. 1996. Multiple lipoprotein abnormalities in type I diabetic patients with renal disease. Diabetes 45:974–979.PubMedCrossRefGoogle Scholar
  129. 129.
    Chen YD, Howard J, Huang V, Kraemer FB, Reaven GM. 1980. Dissociation between plasma triglyceride concentration and tissue lipoprotein lipase deficiency in insulin-deficient rats. Diabetes 29:643–647.PubMedCrossRefGoogle Scholar
  130. 130.
    Bar-on H, Levy E, Oschry Y, Ziv E, Shafrir E. 1984. Removal defect of very-low-density lipoproteins from diabetic rats. Biochim Biophys Acta 793:115–118.PubMedCrossRefGoogle Scholar
  131. 131.
    O’Looney P, Irwin D, Briscoe P, Vahouny GV. 1985. Lipoprotein composition as a component in the lipoprotein clearance defect in experimental diabetes. J Biol Chem 260:428–432.PubMedGoogle Scholar
  132. 132.
    Breslow JL. 1989. Genetic basis of lipoprotein disorders. J Clin Invest 84:373–380.PubMedCrossRefGoogle Scholar
  133. 133.
    Levy E, Shafrir E, Ziv E, Bar-On H. 1985. Composition, removal and metabolic fate of chylomicrons derived from diabetic rats. Biochim Biophys Acta 834:376–385.PubMedCrossRefGoogle Scholar
  134. 134.
    Saheki S, Hitsumoto Y, Murase M, Takeuchi N, Uchida K. 1993. In vitro degradation of very low density lipoprotein from diabetic patients by lipoprotein lipase. Clin Chim Acta 217:105–114.PubMedCrossRefGoogle Scholar
  135. 135.
    Sambandam N, Abraham MA, St Pierre E, Al-Atar O, Cam MC, Rodrigues B. 1999. Localization of lipoprotein lipase in the diabetic heart: regulation by acute changes in insulin. Arterioscler Thromb Vase Biol 19:1526–1534.CrossRefGoogle Scholar
  136. 136.
    Rio ALD, Sandalio LM, Palma JM, Bueno P, Corpas FJ. 1991. Metabolism of oxygen radicals in peroxisomes and cellular implications. Free Radicals Biol. Med. 557.Google Scholar
  137. 137.
    Rutledge JC, Woo MM, Rezai AA, Curtiss LK, Goldberg IJ. 1997. Lipoprotein lipase increases lipoprotein binding to the artery wall and increases endothelial layer permeability by formation of lipolysis products. Circ Res 80:819–828.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Thomas Chacko Pulinilkunnil
    • 1
  • Nandakumar Sambandam
    • 1
  • Brian Rodrigues
    • 1
  1. 1.Division of Pharmacology and Toxicology, Faculty of Pharmaceutical SciencesThe University of British ColumbiaVancouverCanada

Personalised recommendations