, Volume 18, Issue 1, pp 65–68 | Cite as

Effect of insulin treatment on prostacyclin in experimental diabetes

  • H. E. Harrison
  • A. H. Reece
  • M. Johnson


Diabetic patients have a high susceptibility to microvascular complications, atherosclerosis and thrombosis. Platelet hyperreactivity possibly related to an imbalance in arachidonic acid metabolism may be involved. Aortic rings or renal cortex produced a potent inhibitor of platelet aggregation, identified as prostacyclin (PGI2). Release of PGI2 by tissues from streptozotocin — diabetic rats (aorta: 0.07±0.1 ng/ mg wet weight; renal cortex 0.004±0.001 ng/mg wet weight) was significantly depressed when compared with controls (aorta: 0.26±0.07 ng/mg wet weight; renal cortex: 0.009±0.001 ng/mg wet weight). Treatment of diabetic animals with insulin for 8 days restored PGI2 production to normal. The finding that PGI2 is depressed in the aorta and in the kidney, tissues which develop angiopathy, and that this is normalised by insulin, suggests that impaired PGI2 production, perhaps associated with platelet hyperreactivity may play a role in the vascular complications of diabetes.

Key words

Streptozotocin diabetic rats prostacyclin aorta renal cortex insulin treatment 


  1. 1.
    Keen, H.: Glucose intolerance, diabetes mellitus and athersclerosis prospects for prevention. Postgrad. Med. J.52, 445–457 (1976)PubMedGoogle Scholar
  2. 2.
    Goodale, F., Daou, A. S., Florentin, R., Lee, K. T., Gittelsohn, A.: Chemico-anatomic studies of arteriosclerosis and throm bosis in diabetics. I. Coronary artery wall thickness, thrombosis and myocardial infarction in autopsied North Americans. Exp. Mol. Pathol.1, 352–363 (1962)Google Scholar
  3. 3.
    Heath, H., Brigden, W. D., Canever, J. V., Pollock, J., Hunter, P. R., Kelsey, J., Bloom, A.: Platelet adhesion and aggregation in relation to diabetic retinopathy. Diabetologia7, 308–315 (1971)PubMedGoogle Scholar
  4. 4.
    Halushka, P. V., Lurie, D., Colwell, J. A.: Increased synthesis of Prostaglandin — E — like material by platelets from patients with diabetes mellitus. N. Engl. J. Med.297, 1306–1310 (1977)PubMedGoogle Scholar
  5. 5.
    Harrison, H. E., Reece, A. H., Johnson, M.: Decreased vascular prostacyclin in experimental diabetes. Life Sci.23, 351–356 (1978)PubMedGoogle Scholar
  6. 6.
    Johnson, M., Reece, A. H., Harrison, H. E.: Decreased vascular prostacyclin in experimental diabetes. Adv. Pharmacol. Chemother.4, 865 (1979)Google Scholar
  7. 7.
    Barham, D., Trinder, P.: An improved colour reagent for the determination of blood glucose by the oxidase system. Analyst97, 142–145 (1972)PubMedGoogle Scholar
  8. 8.
    Bunting, S., Moncada, S., Reed, P., Salmon, J. A., Vane, J. R.: An antiserum to 5, 6-dihydro prostacyclin (PGI1) which also binds prostacyclin. Prostaglandins15, 565–573 (1978)PubMedGoogle Scholar
  9. 9.
    Moncada, S., Gryglewski, R., Bunting, S., Vane, J. R.: A lipid peroxide inhibits the enzyme in blood vessel microsomes that generates from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregation. Prostaglandins12, 715–736 (1976)PubMedGoogle Scholar
  10. 10.
    Dusting, G. J., Moncada, S., Vane, J. R.: Prostacyclin (PGX) is the endogenous metabolite responsible for relaxation of coro nary arteries by arachidonic acid. Prostaglandins13, 3–15 (1977)PubMedGoogle Scholar
  11. 11.
    Kwaan, H. C., Colwell, J. A., Cruz, S., Suwanwela, N., Dobbie, J. G.: Increased platelet aggregation in diabetes mellitus. J. Lab. Clin. Med.80, 236–246 (1972)PubMedGoogle Scholar
  12. 12.
    Breddin, K., Grun, H., Krzywarek, H. R., Schremmer, W. P.: On the measurement of spontaneous platelet aggregation: the platelet aggregation test. III. Methods and first clinical results. Thromb. Haemostas.35, 669–691 (1976)Google Scholar
  13. 13.
    Ferguson, J. C., Mackay, N., Philip, J. A. D., Sumner, D. J.: Determination of platelet and fibrinogen half life with75 (Se) selenomethionine: studies in normal and diabetic subjects. Clin. Sci. Mol. Med.49. 115–120 (1975)PubMedGoogle Scholar
  14. 14.
    McGuire, M. B., Ward, J. D., Russell, R. G. G., Best, L. C., Preston, F. E.: Increased malonyldialdehyde productionin vitro by platelets from patients with diabetes mellitus. (Abstract), p. 531. XVII Congress of Haematology, Paris, July 1978Google Scholar
  15. 15.
    Preston, F. E., Ward, J. D., Marcola, B. H., Porter, N. R., Timperley, W. R., O'Malley, B. C.: Elevatedβ-thromboglobulin levels and circulating platelet aggregates in diabetic microangiopathy. Lancet1978 I, 238–239Google Scholar
  16. 16.
    Needleman, P., Moncada, S., Bunting, S., Vane, J. R., Hamberg, M., Samuelson, B.: Identification of an enzyme in platelet microsomes which generates Thromboxane A2 from prostaglandin endoperoxides. Nature261, 558–560 (1976)PubMedGoogle Scholar
  17. 17.
    Hamberg, M., Samuelson, B.: Detection and isolation of an endoperoxide intermediate in prostaglandin synthesis. Proc. Natl. Acad. Sci. USA70, 899–903 (1973)PubMedGoogle Scholar
  18. 18.
    Herman, A. G., Moncada, S., Vane, J. R.: Formation of prostacyclin (PGI2) by different layers of the arterial wall. Arch. Int. Pharmacodyn. Ther.227, 162–163 (1977)PubMedGoogle Scholar
  19. 19.
    Needleman, P., Minkes, M., Raz, A.: Thromboxanes: Selective biosynthesis and distinct biological properties. Science193, 163–165 (1976)PubMedGoogle Scholar
  20. 20.
    Hamberg, M., Svensson, J., Samuelson, B.: Thromboxanes — a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc. Natl. Acad. Sci USA72, 2994–2998 (1975)PubMedGoogle Scholar
  21. 21.
    Szczeklik, A., Gryglewski, R. J., Wizankowki, R., Musial, J., Pieton, R., Mruk, J.: Circulatory and antiplatelet effects of intravenous prostacyclin in healthy men. Pharmacol. Res. Commun.10, 545–556 (1978)PubMedGoogle Scholar
  22. 22.
    Moncada, S., Gryglewski, R., Bunting, S., Vane, J. R.: An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature263, 663–665 (1976)PubMedGoogle Scholar
  23. 23.
    Johnson, M., Harrison, H. E., Raftery, A. T., Elder, J. B.: Vascular prostacyclin may be reduced in diabetes in man. Lancet1979 I, 325–326Google Scholar
  24. 24.
    Ross, R., Glomset, J., Kariya, B., Harker, L.: A platelet dependent factor that stimulates the proliferation of arterial smooth muscle cellsin vitro. Proc. Natl. Acad. Sci. USA71, 1207–1210 (1974)PubMedGoogle Scholar
  25. 25.
    Tennenbaum, J., Nies, A. S., Aulsebrook, K., Sweetman, B., Oates, J. A.: Release of prostaglandins from rat renal papilla in vitro: Effect of glucose concentration. Fed. Proc.35, 223 (1976)Google Scholar
  26. 26.
    Praag, D. V., Farber, S. J.: Effect of increased osmolality on prostaglandin metabolism in rabbit kidney. Fed. Proc.35, 223 (1976)Google Scholar
  27. 27.
    Fox, C. S., Darby, S. C., Ireland, J. T., Sönksen, P. H.: Blood glucose control and glomerular capillary basement membrane thickening in experimental diabetes. Br. Med. J.1977 II, 605–607Google Scholar
  28. 28.
    Engerman, R., Bloodworth, J. M. B., Nelson, S.: Relationship of microvascular disease in diabetes to metabolic control. Diabetes26, 760–769 (1977)PubMedGoogle Scholar
  29. 29.
    Scharp, D., Krupin, T., Waltman, S., Oestrich, C., Feldman, S., Ballinger, W., Becker, B.: Relationship of abnormal insulin release to fluorophotometry in experimental diabetes. Diabetes27, 435 (1978)Google Scholar
  30. 30.
    Kohner, E. M., Fraser, T. R., Joplin, G. F., Oakley, N. W.: The effect of control on diabetic retinopathy. In: The treatment of diabetic retinopathy. Goldberg. M. F., Fine, S. L. (Eds.), p. 119–124. Washington: US Public Health Service No. 1890 1969Google Scholar
  31. 31.
    Takazakura, E., Nakamoto, Y., Hayakawa, H., Kawai, K., Muramoto, S., Yoshida, K., Shimizu, M., Shinoda, A., Takeuchi, J.: Onset and progression of diabetic glomerulopathy. Diabetes24, 1–9 (1975)PubMedGoogle Scholar
  32. 32.
    Mauer, S. M., Barbara, J., Vernier, R. L., Kjellstrand, C. M., Buselmeier, T. J., Simmons, R. L., Najarian, J. S., Goetz, F. C.: Development of diabetic vascular lesions in normal kidneys transplanted into patients with diabetes mellitus. N. Engl. J. Med.295, 916–920 (1976)PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • H. E. Harrison
    • 1
  • A. H. Reece
    • 1
  • M. Johnson
    • 1
  1. 1.Department of BiologyImperial Chemical IndustriesMacclesfieldEngland

Personalised recommendations