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Insulin concentrations and insulin sensitivity after short-term amiloride in healthy subjects

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Abstract

We have evaluated the short-term effects of amiloride on insulin action in vivo, since amiloride is known to impair insulin action in vitro.

Seven healthy subjects were treated according to a randomized, double-blind, cross-over protocol. The treatment periods were 3 days each with amiloride 15 mg daily and placebo. Insulin action on glucose turnover was assessed directly after each treatment period with the hyper-insulinaemic euglycaemic glucose clamp technique.

At the two insulin concentrations studied (∼ 30 mU·l−1 and ∼ 200 mU·l−1), the glucose infusion rate required to maintain constant euglycaemia did not differ after either amiloride or placebo. The rates of glucose production and utilization were also similar, whereas the so-called insulin sensitivity index at the lower insulin concentration was significantly reduced (by about 15 %) after amiloride. Moreover, amiloride produced significantly higher fasting insulin and C-peptide concentrations, whereas fasting glucose and NEFA concentrations were unaltered.

In conclusion, these data suggest that short-term amiloride slightly impairs insulin sensitivity with respect to glucose uptake. However, overall glucose homoeostasis does not appear to be affected, probably due to a compensatory rise in plasma insulin.

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References

  1. Jeunemaitre X, Charru A, Chatellier G, Degoulet P, Julien J, Plouin, P-F, Corvol P, Ménard J (1988) Long-term metabolic effects of spironolactone and thiazides combined with potassium-sparing agents for treatment of essential hypertension. Am J Cardiol 62: 1072–1077

    Google Scholar 

  2. Gries FA, Kleophas W (1990) Effects of diuretics on insulin secretion and glucose disposal. Horm Metab Res 22 [Suppl]: 33–38

    Google Scholar 

  3. Lowenthal DT, Gould A, Shirk J, Mazzella RN, Affrime MB, Walker F, Onesti G (1980) Effects of amiloride on oral glucose loading, serum potassium, renin and aldosterone in diet-controlled diabetes. Clin Pharmacol Ther 27: 671–676

    Google Scholar 

  4. Davis RJ, Czech MP (1985) Amiloride directly inhibits growth factor receptor tyrosine kinase activity. J Clin Biol Chem 260: 2543–2551

    Google Scholar 

  5. Holland R, Woodgett JR, Hardie DG (1983) Evidence that amiloride antagonises insulin-stimulated protein phosphorylation by inhibiting protein kinase activity. FEBS Lett 154: 269–273

    Google Scholar 

  6. Kadota S, Fantus IG, Deragon G, Guyda HJ, Posner BI (1987) Stimulation of insulin-like growth factor II receptor binding and insulin receptor kinase activity in rat adipocytes. J Biol Chem 262: 8252–8256

    Google Scholar 

  7. Eriksson J, Lönnroth P, Wesslau C, Smith U (1991) Amiloride inhibits insulin sensitivity and responsiveness in rat adipocytes through different mechanisms. Biochem Biophys Res Commun 176: 1277–1284

    Google Scholar 

  8. Pouysségur J, Chambard JC, Franchi A, Paris S, van Obberghen-Schilling E (1982) Growth factor activation of an amiloride-sensitive Na+/H+ exchange system in quiescent fibroblasts: coupling to ribosomal protein S6 phosphorylation. Proc Natl Acad Sci USA 79: 3935–3939

    Google Scholar 

  9. Boquist L (1980) Effects of amiloride on insulin release, serum glucose and insulin, and glucose tolerance of mice. Med Biol 58: 109–111

    Google Scholar 

  10. DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214-E223

    Google Scholar 

  11. Finegood DT, Bergman RN, Vranic M (1987) Estimation of endogenous glucose production during hyperinsulinemic-euglycemic glucose clamps. Diabetes 36: 914–924

    Google Scholar 

  12. Attvall S, Eriksson BM, Fowelin J, von Schenck H, Lager I, Smith U (1987) Early posthypoglycemic insulin resistance in man is mainly an effect of β-adrenergic stimulation. J Clin Invest 80: 437–442

    Google Scholar 

  13. Ashworth L, Gibb I, Alberti KGMM (1992) Hemocue: evaluation of a portable photometric system for determining glucose in whole blood. Clin Chem 38: 1479–1482

    Google Scholar 

  14. Pollare T, Lithell H, Berne C (1989) A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. New Engl J Med 321: 868–873

    Google Scholar 

  15. Veterans Administration Cooperative Study Group on Anti-hypertensive Agents (1985) Propranolol or hydrochlorothiazide alone for the initial treatment of hypertension. IV. Effect on plasma glucose and glucose tolerance. Hypertension 7: 1008–1016

    Google Scholar 

  16. Helderman JH, Elahi D, Andersen DK, Raizes GS, Tobin JD, Shocken D, Andres R (1983) Prevention of the glucose intolerance of thiazide diuretics by maintenance of body potassium. Diabetes 32: 106–111

    Google Scholar 

  17. Falch DK, Schreiner A (1983) The effect of spironolactone on lipid glucose and uric acid levels in blood during long-term administration to hypertensives. Acta Med Scand 213: 27–30

    Google Scholar 

  18. Reaven GM (1988) Banting lecture 1988: role of insulin resistance in human disease. Diabetes 37: 1595–1607

    Google Scholar 

  19. Pears J, Jung RT, Burchell A (1989) Amiloride activation of hepatic microsomal glucose-6-phosphatase; activation of T1? Biochim Biophys Acta 993: 224–227

    Google Scholar 

  20. Svedberg J, Strömblad G, Wirth A, Smith U, Björntorp P (1991) Fatty acids in the portal vein of the rat regulate hepatic insulin clearance. J Clin Invest 88: 2054–2058

    Google Scholar 

  21. Smith AJ, Smith RN (1973) Kinetics and bioavailability of two formulations of amiloride in man. Br J Pharmacol 48: 646–649

    Google Scholar 

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Eriksson, J.W., Fowelin, J. & Urbanavicius, V. Insulin concentrations and insulin sensitivity after short-term amiloride in healthy subjects. Eur J Clin Pharmacol 46, 469–472 (1994). https://doi.org/10.1007/BF00191913

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  • DOI: https://doi.org/10.1007/BF00191913

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