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Effects of insulin on kidney function and sodium excretion in healthy subjects


Insulin action on kidney function was evaluated in 8 healthy subjects, (mean age 27 years) using the euglycaemic clamp technique. Insulin was infused at rates of 0, 20 and 40 mU·min−1·m−2 over consecutive periods of 120 min resulting in plasma insulin concentrations of 8±2, 29±7 and 66±14 mU/l. The renal clearance of 51Cr-EDTA, lithium, sodium and potassium was determined during the last 90 min of each period. Sodium clearance declined with increasing plasma insulin concentrations (1.3±0.4, 1.0±0.3 and 0.5±0.2 ml·min−1·1.73 m−2, p<0.001), while glomerular filtration rate (108±21, 104±21 and 108±20ml·min−1·1.73 m−2) and lithium clearance (a marker of fluid flow rate from the proximal tubules) 29±5, 29±4 and 30±4 ml·min−1·1.73 m−2) remained unchanged. Calculated proximal tubular reabsorption of sodium and water was unchanged, while calculated distal fractional sodium reabsorption increased (95.5±1.5, 96.4±1.2 and 98.1±0.7%, p<0.001). Potassium clearance and plasma potassium concentration declined, whereas plasma aldosterone and plasma renin concentrations were unchanged. In conclusion, elevation of plasma insulin concentration within the physiological range has a marked antinatriuretic action. This effect is located distally to the proximal renal tubules.


  1. 1.

    Feldt-Rasmussen B, Mathiesen ER, Deckert T, Giese J, Christensen NJ, Bent-Hansen L, Nielsen MD (1987) Central role for sodium in the pathogenesis of blood pressure changes independent of angiotensin, aldosterone and catecholamines in Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30: 610–617

    Google Scholar 

  2. 2.

    O'Hare JA (1988) The enigma of insulin resistance and hypertension. Insulin resistance, blood pressure and the circulation. Am J Med 84: 505–510

    Google Scholar 

  3. 3.

    O'Hare JP, Corrall RJM (1988) De natrio diabeticorum. Increased exchangeable sodium in diabetes. Diabetic Med 5: 22–26

    Google Scholar 

  4. 4.

    Landsberg L (1986) Diet, obesity and hypertension. An hypothesis involving insulin, the sympathetic nervous system, and adaptative thermogenesis. Q J Med 61: 1081–1090

    Google Scholar 

  5. 5.

    Reaven GM, Hoffman BB (1987) A role for insulin in the aetiology and course of hypertension. Lancet II: 435–437

    Google Scholar 

  6. 6.

    DeFronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ (1975) The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest 55: 845–855

    Google Scholar 

  7. 7.

    DeFronzo RA, Goldberg M, Agus ZS (1976) The effects of glucose and insulin on renal electrolyte transport. J Clin Invest 58: 83–90

    Google Scholar 

  8. 8.

    Hammerman MR (1985) Interaction of insulin with the renal proximal tubular cell. Am J Physiol 249: F1-F11

    Google Scholar 

  9. 9.

    Baum M (1987) Insulin stimulates volume absorption in the rabbit proximal convoluted tubule. J Clin Invest 79: 1104–1109

    Google Scholar 

  10. 10.

    Lindbjerg IF, Brandt NJ (1964) Indirect determination of the volume of residual urine with 131I-labelled hippuran. Acta Chir Scand 127: 675–680

    Google Scholar 

  11. 11.

    Holstein-Rathlou N-H, Svendsen UG, Leyssac PP (1982) Proximal and distal tubular reabsorption during isotonic volume expansion in patients with essential hypertension as estimated by means of combined 51Cr-labelled EDTA and lithium clearance. Clin Sci 63: 219s-221s

    Google Scholar 

  12. 12.

    Amdisen A (1975) The estimation of lithium in urine. In: Johnson FN (ed) Lithium research and therapy. Academic Press, London, UK, pp 181–195

    Google Scholar 

  13. 13.

    Andersen I, Hannibal S (1983) Analytical and economical optimization of a glucose method with immobilized enzymes. J Automatic Chem 5: 188–192

    Google Scholar 

  14. 14.

    Heding LG (1972) Determination of total serum insulin (IR) in insulin-treated diabetic patients. Diabetologia 8: 260–266

    Google Scholar 

  15. 15.

    Giese J, Damkjær Nielsen M, Kappelgaard AM (1981) Concentrations of active and inactive renin in human plasma: concepts and methodology. In: Sambhi MP (ed) Heterogeneity of Renin and Renin-substrate. Amsterdam, Elsevier/North Holland, pp 205–213

    Google Scholar 

  16. 16.

    Lund JO, Damkjær Nielsen M, Giese J, Gammelgaard PA, Hasner E, Hesse B, Tønnesen KH (1980) Localization of aldosteroneproducing tumours in primary aldosteronism by adrenal and renal vein catheterization. Acta Med Scand 207: 345–351

    Google Scholar 

  17. 17.

    Siegel S (1956) Nonparametric statistics for the behavioral sciences. McGraw-Hill Kogakuska, Tokyo

    Google Scholar 

  18. 18.

    Hollander M, Wolfe DA (1973) Nonparametric statistical methods. John Wiley, New York, USA

    Google Scholar 

  19. 19.

    DeFronzo RA (1981) The effect of insulin on renal sodium metabolism. A review with clinical implications. Diabetologia 21: 165–171

    Google Scholar 

  20. 20.

    Weinsier RL (1971) Fasting — A review with emphasis on the electrolytes. Am J Med 50: 233–240

    Google Scholar 

  21. 21.

    Wen S-F (1974) Micropuncture studies of phosphate transport in the proximal tubule of the dog. The relationship to sodium reabsorption. J Clin Invest 53: 143–153

    Google Scholar 

  22. 22.

    Mizgala CL, Quamme GA (1985) Renal handling of phosphate. Physiol Rev 65: 431–466

    Google Scholar 

  23. 23.

    Gmaj P, Murer H (1986) Cellular mechanisms of inorganic phosphate transport in kidney. Physiol Rev 66: 36–71

    Google Scholar 

  24. 24.

    Moore RD (1983) Effects of insulin upon ion transport. Biochim Biophys Acta 737: 1–49

    Google Scholar 

  25. 25.

    Jørgensen PL (1980) Sodium and potassium ion pump in kidney tubules. Physiol Rev 60: 864–917

    Google Scholar 

  26. 26.

    Madsen KM, Tisher CC (1986) Strucutral-functional relationships along the distal nephron. Am J Physiol 250: F1-F15

    Google Scholar 

  27. 27.

    Rabkin R, Ryan MP, Duckworth WC (1984) The renal metabolism of insulin. Diabetologia 27: 351–357

    Google Scholar 

  28. 28.

    Christiansen JS, Frandsen M, Parving H-H (1981) The effect of intravenous insulin infusion on kidney function in insulin-dependent diabetes mellitus. Diabetologia 20: 199–204

    Google Scholar 

  29. 29.

    Rowe JW, Young JB, Minaker KL, Stevens AL, Pallotta J, Landsberg L (1981) Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes 30: 219–225

    Google Scholar 

  30. 30.

    Izzo J (1983) Cardiovascular hormonal effects of circulating norepinephrine. Hypertension 5: 787–789

    Google Scholar 

  31. 31.

    Airaksinen J, Lahtela JT, Ikaheimo MJ, Sotiniemi EA, Takkunen JT (1985) Intravenous insulin has no effect on myocardial contractility or heart rate in healthy subjects. Diabetologia 28: 649–652

    Google Scholar 

  32. 32.

    Sternheim W, Dalakos TG, Streeten DHP, Fox L, Speller PJ (1982) Action of L-epinephrine on the renin-aldosterone system and on urinary electrolyte excretion in man. Metabolism 31: 979–984

    Google Scholar 

  33. 33.

    DiBona GF (1985) Neural regulation of renal tubular sodium reabsorption and renin secretion. Fed Proc 44: 2816–2822

    Google Scholar 

  34. 34.

    Kirchner KA (1988) Insulin increases loop segment chloride reabsorption in the euglycemic rat. Am J Physiol 255: F 1206-F 1213

    Google Scholar 

  35. 35.

    Thomsen K, Holstein-Rathlou N-H, Leyssac PP (1981) Comparison of three measures of proximal tubular reabsorption: lithium clearance, occlusion time, and micropuncture. Am J Physiol 241: F348-F355

    Google Scholar 

  36. 36.

    Thomsen K (1984) Lithium clearance: A new method for determining proximal and distal tubular reabsorption of sodium and water. Nephron 37: 217–223

    Google Scholar 

  37. 37.

    Skøtt P, Bruun NE, Giese J, Holstein-Rathlou N-H, Leyssac PP (1987) What does lithium clearance measure during osmotic diuresis? Clin Sci 73: 126–127

    Google Scholar 

  38. 38.

    Baines AD, Drangova R, Ho P (1987) a 1-Adrenergic stimulation of renal Na reabsorption requires glucose metabolism. Am J Physiol 253: F810-F815

    Google Scholar 

  39. 39.

    Atherton JC, Green R, Hughes S, McFall V, Sharples JA, Solomon LR, Wilson L (1987) Lithium clearance in man: effects of dietary salt intake, acute changes in extracellular fluid volume, amiloride and frusemide. Clin Sci 73: 645–651

    Google Scholar 

  40. 40.

    Boer WH, Koomans HA, Dorhout Mees EJ (1988) Renal lithium handling during water loading and subsequent d-DAVP-induced anti-diuresis. Eur J Clin Invest 18: 273–278

    Google Scholar 

  41. 41.

    Anderson J, Struthers A, Christofides N, Bloom S (1986) Atrial natriuretic peptide: an endogenous factor enhancing sodium excretion in man. Clin Sci 70: 327–331

    Google Scholar 

  42. 42.

    Hughes JM, Ragsdale V, Felder RA, Chevalier RL, King B, Carey RM (1988) Diuresis and natriuresis during continuous dopamine-1 receptor stimulation. Hypertension 11 [Suppl] I: I-69-I-74

    Google Scholar 

  43. 43.

    Morice A, Pepke-Zaba J, Loysen E, Lapworth R, Ashby M, Higenbottam T, Brown M (1988) Low dose infusion of atrial natriuretic peptide causes salt and water excretion in normal man. Clin Sci 74: 359–363

    Google Scholar 

  44. 44.

    Williams TDM, Walsh KP, Pitts E, Sutton R, Lightman SL (1988) Rebound increase in plasma renin and vasopressin following graded infusions of atrial natriuretic peptide in man. J Endocr Invest 11: 31–35

    Google Scholar 

  45. 45.

    Velasquez MT, Skelton MM, Cowley AW (1987) Water loading and restriction in essential hypertension. Hypertension 9: 407–414

    Google Scholar 

  46. 46.

    Richards AM, Tonolo G, Montorsi P, Finlayson J, Fraser R, Inglis G, Towrie A, Morton J (1988) Low dose infusions of 26- and 28-amino acid human atrial natriuretic peptides in normal man. J Clin Endocr Met 66: 465–472

    Google Scholar 

  47. 47.

    Solomon LR, Atherton JC, Bobinski H, Green R (1987) Effects of dietary sodium chloride and posture on plasma immunoreactive atrial natriuretic peptide concentrations in man. Clin Sci 72: 201–208

    Google Scholar 

  48. 48.

    Chipperfield AR (1986) The (Na+-K+-Cl)co-transport system. Clin Sci 71: 465–476

    Google Scholar 

  49. 49.

    Rossetti L, Klein-Robbenhaar G, Giebisch G, Smith D, DeFronzo R (1987) Effect of insulin on renal potassium metabolism. Am J Physiol 252: F 60-F 64

    Google Scholar 

  50. 50.

    Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S (1987) Insulin resistance in essential hypertension. N Engl J Med 317: 350–357

    Google Scholar 

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Skøtt, P., Hother-Nielsen, O., Bruun, N.E. et al. Effects of insulin on kidney function and sodium excretion in healthy subjects. Diabetologia 32, 694–699 (1989).

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Key words

  • lithium clearance
  • glomerular filtration rate
  • sodium excretion
  • insulin
  • normal subjects
  • distal renal tubules