Acta Diabetologica

, Volume 32, Issue 3, pp 170–175 | Cite as

Decreased capacity to inhibit platelet hyperactivity and to stabilize prostacyclin of high-density lipoproteins in experimental diabetes

  • I. Ginon
  • C. Talussot
  • G. Ponsin
  • M. Ciavatti


Twenty-eight male Sprague Dawley rats were divided into two groups: a control group (C) of 15 animals and a streptozotocin-induced diabetes group mildly balanced by insulin (D) of 13 animals. After 15 weeks, plasma and high-density lipoprotein (HDL) lipids were determined in each group. Apoprotein A-I concentration was evaluated in HDL fractions. The capacity of the HDL fraction to inhibit thrombin and ADP-induced aggregation of normal platelets was determined for each rat, and in an additional experiment the relation dose-effect of HDL was established. The effect of HDL of the two groups on the stabilization of prostacyclin was compared by aggregation bioassay. After 15 weeks, HDL cholesterol (free+esterified) tended to increase in group D compared with group C (P<0.08). By contrast, apoprotein A-I was very significantly decreased in HDL-D compared with HDL-C (P<0.001). These alterations were accompanied by a significantly decreased capacity of HDL (60 μg/ml platelet suspension) to inhibit ADP-induced aggregation (P<0.0001) in group D compared with group C. Furthermore, HDL-D incubated 45 or 90 min with prostacyclin showed a significantly decreased capacity to stabilize prostacyclin compared with HDL-C (P<0.04;P<0.03, respectively). These alterations in HDL could be involved in thrombosis and atheromatous complications associated with this disease.

Key words

Streptozotocin-induced diabetic rats Highdensity lipoprotein Platelet aggregation Prostacyclin stabilization 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Tall AR, Plasma high density lipoproteins; metabolism and relationship to atherogenesis. J Clin Invest 86:379–384, 1990PubMedGoogle Scholar
  2. 2.
    Aviram M, Brook JG, Platelet interaction with high and low density poproteins. Atherosclerosis 46:259–268, 1983PubMedGoogle Scholar
  3. 3.
    Curtiss LK, Plow EF, Interactions of plasma lipoproteins with human platelets. Blood 64:365–374, 1984PubMedGoogle Scholar
  4. 4.
    Hassall DGL, Forrest RA, Bruckdorfer KR, Marenah CB, Turner C, Cortese N, Miller E, Lewis B, Influence of plasma lipoproteins on platelet aggregation in a normal male population. Arteriosclerosis 3:332–338, 1983PubMedGoogle Scholar
  5. 5.
    Yui Y, Aoyama T, Morishita H, Takahashi M, Takatsu Y, Kawai C, Serum prostacyclin stabilizing factor is identical to apolipoprotein A-I. J Clin Invest 82:803–807, 1988PubMedGoogle Scholar
  6. 6.
    Watanabe J, Wolthmann HJ, Klein RL, Colwell JA, Lopes-Virella MF, Enhancement of platelet aggregation by low density lipoproteins from IDDM patients. Diabetes 37:1652–1657, 1988PubMedGoogle Scholar
  7. 7.
    Valentovic MA, Lubway WC, Impact of insulin or tolbutamide treatment on 14C arachidonic acid conversion to prostacyclin and/or thromboxane in lungs, aortas, and platelets of streptozotocin-induced diabetic rats. Diabetes 32:846–851, 1983PubMedGoogle Scholar
  8. 8.
    Bar-on H, Roheim P, Eder H, Serum lipoproteins and apolipoproteins in rats with streptozotocin-induced diabetes. J Clin Invest 57:714–721, 1976PubMedGoogle Scholar
  9. 9.
    Colette C, Pares-Herbute N, Monnier LH, Cartry E, Platelet function in type I diabetes: effects of supplementation with large dose of vitamin E. Am J Clin Nutr 47:256–261, 1988PubMedGoogle Scholar
  10. 10.
    Burnstein M, Scholnick H, Morfin R, Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res 11:583–595, 1970PubMedGoogle Scholar
  11. 11.
    Talussot C, Ponsin G, Cholesterol-induced alteration of apolipoprotein AI conformation in reassembled high density lipoproteins. Biochimie 73:1173–1178, 1991CrossRefPubMedGoogle Scholar
  12. 12.
    Leclerq M, Bourgeay-Causse M, Une methode simple, fiable et rapide: dosage simultané du rétinol et du tocopherol sériques par chromatographie liquide haute performance. Rev Inst Pasteur 14:475–496, 1981Google Scholar
  13. 13.
    Folch JM, Lees M, Sloane SGM, A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–507, 1957PubMedGoogle Scholar
  14. 14.
    Omodeo Sale F, Maechesini S, Fishman P, Berra B, A sensitive enzymatic assay for determination of cholesterol in lipid extracts. Anal Biochem 142:347–350, 1984CrossRefPubMedGoogle Scholar
  15. 15.
    France D, Hughes T, Miserendino R, Spirito S, Babiak J, Eskesen B, Tapparelli C, Paterniti J, Nonimmunochemical quantitation of mammalian apolipoprotein A-I in whole serum or plasma by non reducing gel electrophoresis. J Lipid Res 30: 1997–2004, 1989PubMedGoogle Scholar
  16. 16.
    Aoyama T, Yui Y, Morishita H, Kawai C, Prostaglandin I2 half life regulated by high density lipoproteins is decreased in acute myocardial infarction and unstable angina pectoris. Circulation 81:1784–1791, 1990PubMedGoogle Scholar
  17. 17.
    Parthasarathy S, Barnett J, Fong LG, High density lipoprotein inhibits the oxidative modification of low density lipoprotein. Biochim Biophys Acta 1044:275–283, 1990PubMedGoogle Scholar
  18. 18.
    Colwell J, Lopes-Virella M, A review of the development of large vessel disease in diabetes mellitus. N Engl J Med 85 (Suppl 5A):113–118, 1988Google Scholar
  19. 19.
    Nikkila EA, Hermila P, Serum lipids and lipoproteins in insulin treated diabetes. Demonstration of increased high density lipoprotein concentrations. Diabetes 27:1078–1086, 1978PubMedGoogle Scholar
  20. 20.
    Sagel J, Colwell JA, Crook L, Liamins M, Increased platelet aggregation in early diabetes mellitus. Ann Intern Med 82: 733–738, 1975PubMedGoogle Scholar
  21. 21.
    Weisgraber KH, Mahley RW, Characterization of rat plasma lipoproteins. In: Lewis L, Naito H (eds) Handbook of electrophoresis. CRC Press, Boca Raton, Florida, pp 103–132, 1983Google Scholar
  22. 22.
    Davenas E, Ciavatti M, Nordoy A, Renaud S, Effects of dietary lipids on behaviour, lipid biosynthesis and lipid composition in rat platelets. Biochim Biophys Acta 793:278–286, 1984PubMedGoogle Scholar
  23. 23.
    Desai K, Bruckdorfer R, Hutton RA, Owen JS, Binding of apo-E rich high density lipoprotein particles by saturables sites on human blood platelets inhibits agonist-induced platelet aggregation. J Lipid Res 30:831–840, 1989PubMedGoogle Scholar
  24. 24.
    Shattil SJ, Anaya-Galindo R, Bennett J, Colman RW, Cooper RA, Platelet hypersensitivity induced by cholesterol incorporation. J Clin Invest 53:636–643, 1975Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • I. Ginon
    • 1
  • C. Talussot
    • 1
  • G. Ponsin
    • 1
  • M. Ciavatti
    • 1
  1. 1.Inserm U 63Bron-LyonFrance

Personalised recommendations