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Diabetologia

, Volume 28, Issue 9, pp 671–676 | Cite as

Acetyl-salicylic acid impairs insulin-mediated glucose utilization and reduces insulin clearance in healthy and non-insulin-dependent diabetic man

  • P. R. Bratusch-Marrain
  • H. Vierhapper
  • M. Komjati
  • W. K. Waldhäusl
Originals

Summary

The effect of acetyl-salicylic acid (ASA, 3 g per day for 3 days) on glucose utilization and insulin secretion was studied in healthy volunteers and Type 2 diabetic patients using the hyperglycaemic and euglycaemic insulin clamp technique. When in healthy subjects arterial plasma glucose was acutely raised and maintained at +7 mmol/l above fasting level, the plasma insulin response was enhanced by ASA (70±7 vs. 52±7mU/l), whereas the plasma C-peptide response was identical. Despite higher insulin concentrations, glucose utilization was not significantly altered (control, 61±7; ASA, 65±6μmol·kg−1·min−1) indicating impairment of tissue sensitivity to insulin by ASA. Inhibition of prostaglandin synthesis was not likely to be involved in the effect of ASA, since insulin response and glucose utilization were unchanged following treatment with indomethacin. In the euglycaemic insulin (1 mU·kg−1·min−1) clamp studies, glucose utilization was unaltered by ASA despite higher insulin concentrations achieved during constant insulin infusion (103±4vs. 89±4mU/l). In Type 2 diabetic patients, fasting hyperglycaemia (10.6 ±1.1 mmol/l) and hepatic glucose production (15±2 μmol·kg−1·min−1) fell upon ASA treatment (8.6±0.7 mmol/l; 13±1 μmol·kg−1· min−1). During the hyperglycaemic clamp study, the plasma response of insulin, but not of C-peptide, was enhanced by ASA, whereas tissue sensitivity to insulin was reduced by 30 percent. It is concluded that in healthy and Type 2 diabetic man, ASA impairs tissue sensitivity to the action of insulin. This effect is counterbalanced by an augmented plasma insulin response to glucose, which results from a reduced insulin clearance rate. In Type 2 diabetic patients, the reduction in hepatic glucose production may be responsible for the amelioration of hyperglycaemia following ASA treatment.

Key words

Acetyl-salicylic acid indomethacin glucose utilization insulin sensitivity insulin secretion insulin clearance hepatic glucose production Type 2 diabetes 

References

  1. 1.
    Robertson AP (1983) PGE, carbohydrate homeostasis, and insulin secretion. A suggested resolution of the controversy. Diabetes 32: 231–234PubMedCrossRefGoogle Scholar
  2. 2.
    Newman WP, Brodows RG (1982) Metabolic effects of prostaglandin E2 infusion in man: possible adrenergic mediation. J Clin Endocrinol Metab 55: 496–501PubMedCrossRefGoogle Scholar
  3. 3.
    Field JB, Boyle C, Remer A (1967) Effect of salicylate infusion on plasma-insulin and glucose tolerance in healthy persons and mild diabetics. Lancet 1: 1191–1194PubMedCrossRefGoogle Scholar
  4. 4.
    Micossi P, Pontiroli AE, Baron SH, Tamayo RC, Lengel F, Bevilacqua M, Raggi U, Norbiato G, Foà PP (1978) Aspirin stimulates insulin and glucagon secretion and increases glucose tolerance in normal and diabetic subjects. Diabetes 27: 1196–1204PubMedCrossRefGoogle Scholar
  5. 5.
    Newman WP, Brodows RG (1983) Aspirin causes tissue insensitivity to insulin in normal man. J Clin Endocrinol Metab 57: 1102–1106PubMedCrossRefGoogle Scholar
  6. 6.
    Prince RL, Larkins RG, Alford FP (1981) The effect of acetylsalicylic acid on plasma glucose and the response of glucose regulatory hormones to intravenous glucose and arginine in insulin-treated diabetics and normal subjects. Metabolism 30: 293–298PubMedCrossRefGoogle Scholar
  7. 7.
    Widström A (1977) Influence of indomethacin on glucose-induced insulin response in normal man — role of prostaglandins in the rapid insulin release? Horm Metab Res 9: 172–175PubMedCrossRefGoogle Scholar
  8. 8.
    Topol E, Brodows RG (1980) Effects of indomethacin on acute insulin release in man. Diabetes 29: 379–382PubMedCrossRefGoogle Scholar
  9. 9.
    Vierhapper H, Bratusch-Marrain P, Waldhäusl W (1980) Unchanged arginine-induced stimulation of insulin, glucagon, growth hormone and prolactin after pretreatment with indomethacin in normal man. J Clin Endocrinol Metab 50: 1131–1134PubMedCrossRefGoogle Scholar
  10. 10.
    DeFronzo RA, Tobin J, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237: E214-E223PubMedGoogle Scholar
  11. 11.
    Bratusch-Marrain PR (1984) Die euglykämische Insulin- und hyperglykämische Clamp-Technik: Methoden zur Bestimmung der Insulinsensitivität der Gewebe und der Glukosesensitivität der BZelle. Infusionsther Klin Ernähr 11: 4–10PubMedGoogle Scholar
  12. 12.
    Wolfe RR, Allsop JR, Burke JF (1979) Glucose metabolism in man: responses to intravenous glucose infusion. Metabolism 28: 210–220PubMedCrossRefGoogle Scholar
  13. 13.
    Somogyi M (1930) A method for the precipitation of blood filtrates for the determination of sugar. J Biol Chem 86: 655–663Google Scholar
  14. 14.
    Waldhäusl W, Bratusch-Marrain P, Gasic S, Korn A, Nowotny P (1979) Insulin production rate following glucose ingestion estimated by splanchnic C-peptide output in normal man. Diabetologia 17: 221–227PubMedCrossRefGoogle Scholar
  15. 15.
    Natelson S (1957) Microtechniques of clinical chemistry for the routine laboratory. Thomas CC (ed). Springfield, Ill, p 332Google Scholar
  16. 16.
    Steele R (1959) Influence of glucose loading and of injected insulin on hepatic glucose output. Ann NY Acad Sci 82: 420–430PubMedCrossRefGoogle Scholar
  17. 17.
    Bratusch-Marrain PR, Smith D, DeFronzo RA (1982) The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 55: 973–982PubMedCrossRefGoogle Scholar
  18. 18.
    Rizza R, Mandarino L, Gerich J (1981) Dose-response characteristics for the effects of insulin on glucose production, glucose utilization and overall glucose metabolism in man: determination using sequential infusion of insulin in conjunction with the glucose clamp technique. Am J Physiol 240: E630-E639PubMedGoogle Scholar
  19. 19.
    Giugliano D, Torella R, Siniscalchi N, Impronta L, D'Onofrio F (1978) The effect of acetylsalicylic acid on insulin response to glucose and arginine in normal man. Diabetologia 14: 359–362PubMedCrossRefGoogle Scholar
  20. 20.
    Vierhapper H, Bratusch-Marrain P, Waldhäusl W, Nowotny P, Panzer S (1983) Increased secretion of insulin but unchanged secretion of growth hormone in hyperglycaemic type II diabetics treated with acetyl-salicylic acid. Clin Endocrinol 18: 613–620CrossRefGoogle Scholar
  21. 21.
    Robertson RP (1981) Prostaglandins, glucose homeostasis and diabetes mellitus. Med Clin North Am 65: 759–771PubMedGoogle Scholar
  22. 22.
    Garcia J, Arata M, Fernández ME, Astolfi E, Basabe JC (1982) Salicylate intoxication and glucose-induced insulin secretion in the rat. Horm Metab Res 14: 553–554PubMedCrossRefGoogle Scholar
  23. 23.
    Metz SA, Robertson RP, Fujimoto WY (1981) Inhibition of prostaglandin E synthesis augments glucose-induced insulin secretion in cultured pancreas. Diabetes 30: 551–557PubMedCrossRefGoogle Scholar
  24. 24.
    Baron SH, Dunbar JC, Foá PP (1982) Lack of effect of acetylsalicylic acid on insulin secretion in isolated hamster islets. Horm Metab Res 14: 437–438PubMedCrossRefGoogle Scholar
  25. 25.
    Bratusch-Marrain PR, Komjati M, Waldhäusl W (1985) Glucose metabolism in non-insulin-dependent diabetic patients with experimental hyperthyroidism. J Clin Endocrinol Metab 60: 1063–1068PubMedCrossRefGoogle Scholar
  26. 26.
    Bratusch-Marrain PR, Waldhäusl WK, Gasic S, Hofer A (1984) Hepatic disposal of biosynthetic human insulin and porcine C-peptide in humans. Metabolism 33: 151–157PubMedCrossRefGoogle Scholar
  27. 27.
    Polonsky KS, Rubenstein AH (1984) C-peptide as a measure of the secretion and hepatic extraction of insulin. Pitfalls and limitations. Diabetes 33: 486–494PubMedCrossRefGoogle Scholar
  28. 28.
    Bratusch-Marrain PR, Waldhäusl WK (1985) Suppression of basal, but not of glucose-stimulated insulin secretion by human insulin in healthy and obese hyperinsulinaemic subjects. Metabolism 34: 188–193PubMedCrossRefGoogle Scholar
  29. 29.
    Vierhapper H, Jörg J, Waldhäusl W (1984) Effect of acetyl-salicylic acid and of indomethacin on diuresis in man: the role of cyclo-oxygenase inhibition. Clin Sci 67: 579–583PubMedGoogle Scholar
  30. 30.
    Miller JD, Ganguli S, Sperling MA (1983) Prostaglandin synthesis inhibitors impair hepatic glucose production in response to glucagon and epinephrine stimulation. Diabetes 32: 439–444PubMedCrossRefGoogle Scholar
  31. 31.
    DeFronzo RA, Simonson D, Ferrannini E (1982) Hepatic and peripheral insulin resistance: a common feature of type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetes mellitus. Diabetologia 23: 313–319PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • P. R. Bratusch-Marrain
    • 1
  • H. Vierhapper
    • 1
  • M. Komjati
    • 1
  • W. K. Waldhäusl
    • 1
  1. 1.Division of Clinical Endocrinology and Diabetes MellitusI. Medizinische UniversitätsklinikViennaAustria

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