Summary
The effects of insulin on renal haemodynamics and renal sodium handling were studied in 10 healthy males. Using the euglycaemic insulin clamp technique, insulin was infused on separate days resulting in two levels of hyperinsulinaemia (41 ± 3 and 90 ± 7 mU/1, respectively). Renal haemodynamics and the proximal and distal tubular sodium handling were studied using inulin, para-amino-hippuric acid, sodium and lithium clearances. Low- and high-dose insulin infusions were followed by a fall in sodium clearance from 1.6 ± 0.1 ml/min to 1.2 ± 0.1 and 1.0 ± 0.1 ml/min, respectively. Both levels of hyperinsulinaemia resulted in increased distal tubular sodium reabsorption. The distal antinatriuretic effect of insulin was associated with dose- and time-dependent decline in proximal tubular sodium reabsorption. The changes in proximal tubular sodium handling occurred without any significant changes in natriuretic factors, such as renal dopamine and plasma atrial natriuretic peptide levels. However, hyperinsulinaemia resulted in time- and dose-dependent increases in renal plasma flow, and renal vasodilatation could, possibly via changes in renal interstitial pressure, have contributed to the fall in the proximal tubular sodium reabsorption. The results also suggest that decreased proximal sodium reabsorption may be a compensatory mechanism counteracting the insulin-induced sodium retention.
Article PDF
Similar content being viewed by others
References
DeFronzo RA, Goldberg M, Agus Z (1976) The effects of glucose and insulin on renal electrolyte transport. J Clin Invest 58: 83–90
Skøtt P, Hother-Nielsen O, Bruun NE, Giese J, Beck-Nielsen H, Parving HH (1989) Effects of insulin on kidney function and sodium excretion in healthy subjects. Diabetologia 32: 694–699
Friedberg CE, van Buren M, Bijlsma JA, Koomans HA (1991) Insulin increases sodium reabsorption in diluting segment in humans: evidence for indirect mediation through hypokalemia. Kidney Int 40: 251–256
Nørgaard K, Jensen T, Skøtt P et al. (1991) Effects of insulin on renal hemodynamics and sodium handling in normal subjects. Scand J Clin Lab Invest 51: 367–376
Abumrad N, Rabin D, Diamond M, Lacy W (1981) Use of a heated superficial hand vein as an alternative site for the measurement of amino acid concentrations and for the study of glucose and alanine kinetics. Metab Clin Exp 30: 936–940
Thomsen K (1984) Lithium clearance: a new method for determining proximal and distal reabsorption of sodium and water. Nephron 37: 217–223
Stenvinkel P, Saggar-Malik AK, Wahrenberg H, Diczfalusy U, Bolinder J, Alvestrand A (1991) Impaired intrarenal dopamine production following intravenous sodium chloride infusion in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 34: 114–118
Andersson U, Sylvén C, Lindvall K, Theodorsson E, Norée L-O (1988) Cardiac function and cardiovascular hormone balance during hemodialysis with special reference to atrial natriuretic peptide. Clin Nephrol 30: 303–307
Heding LP (1975) Radioimmunological determination of human C-peptide in serum. Diabetologia 11: 541–548
Wide L, Axén R, Porath J (1967) Radioimmunosorbent assay for proteins chemical couplings of antibodies to insoluble dextran. Immunochemistry 4: 381–386
Amdisen A (1975) The estimation of lithium in urine. In Johnson IN (ed) Lithium research and therapy. Academic Press, London, pp 181–195
DeFronzo RA, Cooke CR, Andres R, Falonna 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
Gans ROB, Bilo HJG, Nauta JJP, Poop-Snijders C, Heine RJ, Donker AIM (1991) Renal and cardiovascular effects of exogenous insulin in healthy volunteers. Clin Sci 80: 219–225
Baum M (1987) Insulin stimulates volume absorption in the rabbit proximal convoluted tubule. J Clin Invest 79: 1104–1109
Trevisan R, Fioretti P, Semplicini A et al. (1990) Role of insulin and atrial natriuretic peptide in sodium retention in insulintreated IDDM patients during isotonic volume expansion. Diabetes 39: 289–298
Skøtt P, Bruun NE, Giese J, Holstein-Rathlou NH, Leyssac PP (1987) What does lithium clearance measure during osmotic diuresis? Clin Sci 73: 126–127
Koomans HA, Boer WH, Dorhout Mees EJ (1989) Evaluation of lithium clearance as a marker of proximal tubule sodium handling. Kidney Int 36: 2–12
Kirchner KA (1988) Insulin increases loop segment chloride reabsorption in the euglycaemic rat. Am J Physiol 255: F1206-F1213
Rabkin R, Ryan MP, Duckworth WC (1984) The renal metabolism of insulin. Diabetologia 27: 351–357
Moore RD (1983) Effect of insulin upon ion transport. Biochem Biophys Acta 737: 1–49
Jørgensen PL (1980) Sodium and potassium ion pump in kidney tubules. Physiol Rev 60: 864–917
Madsen KM, Tischer TC (1986) Structural-functional relationships along the distal nephron. Am J Physiol 250: 171–1715
Fine LG, Baiene-Dezfooly B, Lowe AG, Hamzeh A, Wells J, Salehmoghaddam S (1985) Stimulation of Na+ /H+ antiport is an early event in hypertrophy of renal proximal tubular cells. Proc Natl Acad Sci USA 82: 1736–1740
Gesek FA, Schoolwerth AC (1991) Insulin increases Na+-H+ exchange activity in proximal tubules from normotensive and hypertensive rats. Am J Physiol 260: 17695–17703
Berretta-Piccoli C, Davies DL, Boddy K et al. (1982) Relation of arterial pressure with body sodium, body potassium and plasma potassium in essential hypertension. Clin Sci 63: 257–270
Boehringer K, Beretta-Piccoli C, Weidmann P, Meier A, Ziegler WH (1982) Pressor factors and cardiovascular pressor responsiveness in lean and overweight normal or hypertensive subjects. Hypertension 4: 697–702
De Chatel R, Weidemann R, Flammer J et al. (1977) Sodium, renin, aldosterone, catecholamines and blood pressure in diabetes mellitus. Kidney Int 12: 412–421
Hall JE, Brands MW, Mizelle HL, Gaillard CA, Hildebrandt DA (1991) Chronic intrarenal hyperinsulinaemia does not cause hypertension. Am J Physiol 260: 17663–17669
Aperia A, Bertorello A, Seri I (1987) Dopamine causes inhibition of Na+-K+-ATPase activity in rat proximal convoluted tubule segments. Am J Physiol 252: 1739–1745
Cohen AJ, McCarthy DM, Stoff JS (1989) Direct hemodynamic effect of insulin in the isolated perfused kidney. Am J Physiol 257: 17580–17585
Alexander WD, Oake RJ (1977) The effect of insulin on vascular reactivity to norepinephrine. Diabetes 26: 611–614
Laakso M, Edelman SV, Brechtel G, Baron AD (1990) Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. J Clin Invest 85: 1844–1852
Haas JA, Granger JP, Knox FG (1986) Effect of renal perfusion pressure on proximal sodium reabsorption from proximal tubules of superficial and deep nephrons. Am J Physiol 250: F425-F429
Haas JA, Hammond TG, Granger JP, Blaine EH, Knox FG (1984) Mechanism of natriuresis during intrarenal infusion of prostaglandins. Am J Physiol 247: 17475–17479
Rowe JW, Young JB, Minaker KL, Stevens AL, Palotta J, Landsberg L (1981) Effect of insulin and glucose infusion on sympathetic nervous system activity in normal man. Diabetes 30: 219–225
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stenvinkel, P., Bolinder, J. & Alvestrand, A. Effects of insulin on renal haemodynamics and the proximal and distal tubular sodium handling in healthy subjects. Diabetologia 35, 1042–1048 (1992). https://doi.org/10.1007/BF02221679
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02221679