Summary
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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
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
O'Hare JA (1988) The enigma of insulin resistance and hypertension. Insulin resistance, blood pressure and the circulation. Am J Med 84: 505–510
O'Hare JP, Corrall RJM (1988) De natrio diabeticorum. Increased exchangeable sodium in diabetes. Diabetic Med 5: 22–26
Landsberg L (1986) Diet, obesity and hypertension. An hypothesis involving insulin, the sympathetic nervous system, and adaptative thermogenesis. Q J Med 61: 1081–1090
Reaven GM, Hoffman BB (1987) A role for insulin in the aetiology and course of hypertension. Lancet II: 435–437
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
DeFronzo RA, Goldberg M, Agus ZS (1976) The effects of glucose and insulin on renal electrolyte transport. J Clin Invest 58: 83–90
Hammerman MR (1985) Interaction of insulin with the renal proximal tubular cell. Am J Physiol 249: F1-F11
Baum M (1987) Insulin stimulates volume absorption in the rabbit proximal convoluted tubule. J Clin Invest 79: 1104–1109
Lindbjerg IF, Brandt NJ (1964) Indirect determination of the volume of residual urine with 131I-labelled hippuran. Acta Chir Scand 127: 675–680
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
Amdisen A (1975) The estimation of lithium in urine. In: Johnson FN (ed) Lithium research and therapy. Academic Press, London, UK, pp 181–195
Andersen I, Hannibal S (1983) Analytical and economical optimization of a glucose method with immobilized enzymes. J Automatic Chem 5: 188–192
Heding LG (1972) Determination of total serum insulin (IR) in insulin-treated diabetic patients. Diabetologia 8: 260–266
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
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
Siegel S (1956) Nonparametric statistics for the behavioral sciences. McGraw-Hill Kogakuska, Tokyo
Hollander M, Wolfe DA (1973) Nonparametric statistical methods. John Wiley, New York, USA
DeFronzo RA (1981) The effect of insulin on renal sodium metabolism. A review with clinical implications. Diabetologia 21: 165–171
Weinsier RL (1971) Fasting — A review with emphasis on the electrolytes. Am J Med 50: 233–240
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
Mizgala CL, Quamme GA (1985) Renal handling of phosphate. Physiol Rev 65: 431–466
Gmaj P, Murer H (1986) Cellular mechanisms of inorganic phosphate transport in kidney. Physiol Rev 66: 36–71
Moore RD (1983) Effects of insulin upon ion transport. Biochim Biophys Acta 737: 1–49
Jørgensen PL (1980) Sodium and potassium ion pump in kidney tubules. Physiol Rev 60: 864–917
Madsen KM, Tisher CC (1986) Strucutral-functional relationships along the distal nephron. Am J Physiol 250: F1-F15
Rabkin R, Ryan MP, Duckworth WC (1984) The renal metabolism of insulin. Diabetologia 27: 351–357
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
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
Izzo J (1983) Cardiovascular hormonal effects of circulating norepinephrine. Hypertension 5: 787–789
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
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
DiBona GF (1985) Neural regulation of renal tubular sodium reabsorption and renin secretion. Fed Proc 44: 2816–2822
Kirchner KA (1988) Insulin increases loop segment chloride reabsorption in the euglycemic rat. Am J Physiol 255: F 1206-F 1213
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
Thomsen K (1984) Lithium clearance: A new method for determining proximal and distal tubular reabsorption of sodium and water. Nephron 37: 217–223
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
Baines AD, Drangova R, Ho P (1987) a 1-Adrenergic stimulation of renal Na reabsorption requires glucose metabolism. Am J Physiol 253: F810-F815
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
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
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
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
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
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
Velasquez MT, Skelton MM, Cowley AW (1987) Water loading and restriction in essential hypertension. Hypertension 9: 407–414
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
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
Chipperfield AR (1986) The (Na+-K+-Cl−)co-transport system. Clin Sci 71: 465–476
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
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
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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). https://doi.org/10.1007/BF00274259
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00274259