Advertisement

Diabetologia

, Volume 21, Issue 3, pp 165–171 | Cite as

The effect of insulin on renal sodium metabolism

A review with clinical implications
  • R. A. DeFronzo
Review Articles

Summary

Data are discussed which demonstrate that insulin plays an important role in sodium metabolism. The primary action of insulin on sodium balance is exerted on the kidney. Increases in plasma insulin concentration within the physiological range stimulate sodium reabsorption by the distal nephron segments and this effect is independent of changes in circulating metabolites or other hormones. Several clinical situations are reviewed: sodium wasting in poorly controlled diabetics, natriuresis of starvation, anti-natriuresis of refeeding and hypertension of obesity, in which insulin-mediated changes in sodium balance have been shown to play an important pathophysiological role.

Key words

Insulin sodium kidney diabetes obesity hypertension 

References

  1. 1.
    Atchley DW, Loeb RF, Richards DW, Benedict EM, Driscoll ME (1933) On diabetic acidosis. J Clin Invest 12: 297–326Google Scholar
  2. 2.
    Miller JH, Bogdonoff MD (1954) Antidiuresis associated with administration of insulin. J Appl Physiol 6: 509–512Google Scholar
  3. 3.
    Veverbrants E, Arky RA (1969) Effects of fasting and refeeding. I. Studies on sodium, potassium, and water excretion on a constant electrolyte and fluid intake. J Clin Endocrinol Metab 29: 55–62Google Scholar
  4. 4.
    Hoffman RS, Martino JA, Wahl G, Arky RA (1960) Effects of fasting and refeeding. II. Tubular sites of sodium reabsorption and effects of oral carbohydrate on potassium, calcium, and phosphate excretion. J Lab Clin Med 74: 915–926Google Scholar
  5. 5.
    Kolanowski J, deGasparo M, Desmecht P, Crabbe J (1972) Further evaluation of the role of insulin in sodium retention associated with carbohydrate administration after a fast in the obese. Eur J Clin Invest 2: 439–444Google Scholar
  6. 6.
    Herrera FC, Whittembury G, Planchard A (1963) Effect of insulin on short-circuit current across isolated frog skin in the presence of calcium and magnesium. Biochim Biophys Acta 66: 170–172Google Scholar
  7. 7.
    Andre R, Crabbe J (1966) Stimulation by insulin of active sodium transport by toadskin: influence of aldosterone and vasopressin. Arch Int Physiol Biochim 74: 538–540Google Scholar
  8. 8.
    Crabbe J, Francois B (1967) Stimulation par l'insuline du transport actif de sodium à travers des membranes epitheliales du crapaud, Bufo marinus. Ann Endocrinol 28: 713–715Google Scholar
  9. 9.
    Francois B, deGasparo M, Crabbe J (1969) Interaction between isolated amphibian skin and insulin. Arch Int Physiol Biochim 77: 527–530Google Scholar
  10. 10.
    Herrera FC (1965) Effect of insulin on short-circuit current and sodium transport across toad urinary bladder. Am J Physiol 209: 819–824Google Scholar
  11. 11.
    DeFronzo RA, Goldberg M, Agus Z (1976) The effects of glucose and insulin on renal electrolyte transport. J Clin Invest 58: 83–90Google Scholar
  12. 12.
    DeFronzo RA, Tobin J, Andres R (1979) The glucose clamp technique. A method for the quantification of beta cell sensitivity to glucose and of tissue sensitivity to insulin. Am J Physiol 237: E214-E223Google Scholar
  13. 13.
    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: 845–855Google Scholar
  14. 14.
    Schloeder FX, Stinebaugh BJ (1970) Renal tubular sites of natriuresis of fasting and glucose-induced sodium conservation. Metab (Clin Exp) 19: 1119–1128Google Scholar
  15. 15.
    Nizet A, Lefebvre P, Crabbe J (1971) Control by insulin of sodium, potassium, and water excretion by the isolated dog kidney. Pfluegers Arch Eur J Physiol 323: 11–20Google Scholar
  16. 16.
    DeFronzo RA, Sherwin RS, Dillingham M, Hendler R, Tamborlane WT, Feiig P (1978) Influence of basal insulin and glucagon secretion on potassium and sodium metabolism. J Clin Invest 61: 472–479Google Scholar
  17. 17.
    Saudek CD, Boulter PR, Knopp RH, Arky RA (1974) Sodium retention accompanying insulin treatment of diabetes mellitus. Diabetes 23: 240–246Google Scholar
  18. 18.
    Kolanowski J, Pizaro MA, deGasparo M, Desmecht P, Harvengt C, Crabbe J (1970) Influence of fasting on adrenocortical and pancreatic islet response to glucose loads in the obese. Eur J Clin Invest 1: 25–31Google Scholar
  19. 19.
    Kolanowski J, Salvador G, Desmecht P, Henquin JC, Crabbe J (1977) Influence of glucagon on natriuresis and glucose-induced sodium retention in the fasting obese subject. Eur J Clin Invest 7: 167–175Google Scholar
  20. 20.
    Kolanowski J, Bodson A, Desmecht P, Bemelmans S, Stein F, Crabbe J (1978) On the relationship between ketonuria and natriuresis during fasting and upon refeeding in obese patients. Eur J Clin Invest 8: 277–282Google Scholar
  21. 21.
    Boulter PR, Hoffman RS, Arky RA (1973) Pattern of sodium excretion accompanying starvation. Metabolism 22: 675–682Google Scholar
  22. 22.
    Sigler MH (1975) The mechanism of the natriuresis of fasting. J Clin Invest 55: 377–387Google Scholar
  23. 23.
    Weinsier RL (1971) Fasting — a review with emphasis on the electrolytes. Am J Med 50: 233–240Google Scholar
  24. 24.
    Bloom WL, Mitchell W Jr (1960) Salt excretion of fasting patients. Arch Intern Med 106: 321–327Google Scholar
  25. 25.
    Stinebaugh FJ, Schloeder FX (1966) Studies on the natriuresis of fasting. I. Effect of pre-fast intake. Metabolism 15: 828–837Google Scholar
  26. 26.
    Schloeder FX, Stinebaugh BJ (1965) Electrolyte excretion in subjects fasting in tropical environment. Arch Intern Med 116: 866–870Google Scholar
  27. 27.
    Stinebaugh BJ, Schloeder FX (1966) Studies on the natriuresis of fasting. II. Relationship to acjdosis. Metabolism 15: 838–846Google Scholar
  28. 28.
    Hoffman RS, Martino JA, Wahl G, Arky RA (1971) Fasting and refeeding. III. Antinatriuretic effect of oral and intravenous carbohydrate and its relationship to potassium excretion. Metabolism 20: 1065–1073Google Scholar
  29. 29.
    Cahill CF (1970) Starvation in man. N Engl J Med 282: 668–675Google Scholar
  30. 30.
    Cahill GF Jr. Owen OE, Morgan AP (1968) The consumption of fuels during prolonged starvation. Adv Enzyme Reg 6: 143–150Google Scholar
  31. 31.
    Landsberg L, Young JB (1978) Fasting, feeding, and regulation of the sympathetic nervous system. N Engl J Med 298: 1295–1301Google Scholar
  32. 32.
    Spark RF, Arky RA, Boulter PB, Saudek CD, O'Brian JJ (1975) Renin, aldosterone, and glucagon in the natriuresis of fasting. N Engl J Med 292: 1335–1340Google Scholar
  33. 33.
    Boulter PR, Spark RF, Arky RA (1973) Effect of aldosterone blockade during fasting and refeeding. Am J Clin Nutr 26: 397–402Google Scholar
  34. 34.
    Verdy M, deChamplain J (1968) Fasting in obese females: II. Plasma renin activity and urinary aldosterone. Can Med Assoc J 98: 1034–1037Google Scholar
  35. 35.
    Garnett ES, Cohen H, Nahmias C, Viol G (1973) The roles of carbohydrate, renin, and aldosterone in sodium retention during and after total starvation. Metabolism 22: 867–874Google Scholar
  36. 36.
    O'Brian J, Saudek CD, Spark RF, Arky RA (1974) Glucagoninduced refractoriness to exogenous mineralocorticoid. J Clin Endocrinol Metab 28: 1147–1149Google Scholar
  37. 37.
    Saudek CD, Boulter PR, Arky RA (1973) The natriuretic effect of glucagon. Its role in starvation. J Clin Endocrinol Metab 36: 761–765Google Scholar
  38. 38.
    Levy M, Starr NL (1972) The mechanism of glucagon-induced natriuresis in dogs. Kidney Int 2: 76–84Google Scholar
  39. 39.
    Chinn RH, Brown JJ, Fraser R, Heron SM, Lever AF, Murchison L, Robertson JIS (1970) The natriuresis of fasting: relationship to changes in plasma renin and aldosterone concentrations. Clin Sci 39: 437–455Google Scholar
  40. 40.
    Gersing A, Bloom WL (1962) Glucose stimulation of salt retention in patients with aldosterone inhibition. Metabolism 11: 329–336Google Scholar
  41. 41.
    Bello-Reuss E, Colindres RE, Pastoriza-Munoz E, Mueller RA, Gottschalk CW (1975) Effect of acute unilateral renal denervation in the rat. J Clin Invest 56: 208–217Google Scholar
  42. 42.
    Besarob A, Silva P, Lansberg L, Epstein F (1977) Effect of catecholamines on tubular function in the isolated perfused rat kidney. Am J Physiol 233: F39-F45Google Scholar
  43. 43.
    Mahnensmith R, Thier SO, Cooke CR, Broadus A, DeFronzo RA (1979) Effect of acute metabolic acidemia on renal electrolyte transport in man. Metabolism 28: 831–842Google Scholar
  44. 44.
    Lemann J Jr., Litzow JR, Lennon EJ (1967) Studies of the mechanism by which chronic metabolic acidosis augments calcium excretion in man. J Clin Invest 46: 1318–1328Google Scholar
  45. 45.
    Veverbrants E, Arky RA (1969) Effects of fasting and refeeding. I. Studies on sodium, potassium, and water excretion on a constant electrolyte and fluid intake. J Clin Endocrinol 29: 55–62Google Scholar
  46. 46.
    Alexander J, Dustan HP, Sims EAH, Tarazi RC 1979 Obesity. In: Report of the hypertension task force. NIH Publication 79-1623Google Scholar
  47. 47.
    Chiang BN, Perlman LV, Epstein FH (1969) Overweight and hypertension. Circulation 39: 403–121Google Scholar
  48. 48.
    Tyroler HA, Heyden S, Harnes CG (1975) Weight and hypertension: Evans County studies of blacks and whites. In: Paul O (ed) Epidemilogy and control of hypertension. Stratton International, New York, pp 177–201Google Scholar
  49. 49.
    Kannel WB, Brand N, Skinner JJ (1967) The relation of adiposity to blood pressure and development of hypertension: the Framingham study. Ann Intern Med 67: 48–59Google Scholar
  50. 50.
    Dahl LK, Silver L, Christie RW (1958) The role of salt in the fall of blood pressure accompanying reduction in obesity. N Engl J Med 258: 1186–1192Google Scholar
  51. 51.
    Reisin E, Abel R, Modan M, Silverberg DS, Eliahou HE, Modan B (1978) Effect of weight loss without salt restriction on the reduction of blood pressure in overweight hypertensive patients. N Engl J Med 298: 1–6Google Scholar
  52. 52.
    Martin L (1952) Effect of weight reduction on normal and raised blood pressures in obesity. Lancet 2: 1051–1053Google Scholar
  53. 53.
    Fletcher AP (1954) The effect of weight reduction upon the blood pressure of obese hypertensive women. Q J Med 23: 331–345Google Scholar
  54. 54.
    DeFronzo RA, Soman V, Sherwin RS, Hendler R, Felig P (1978) Insulin binding to monocytes and insulin action in human obesity, starvation, and refeeding. J Clin Invest 62: 204–213Google Scholar
  55. 55.
    Sims EAH, Danforth E, Horton ES, Bray GA, Glennon JA, Salans LB (1973) Endocrine and metabolic effects of experimental obesity in man. Rec Prog Hormone Res 29: 457–487Google Scholar
  56. 56.
    Stanik S, Marcus R (1980) Insulin secretion improves following dietary control of plasma glucose in hyperglycemic obese patients. Metabolism 29: 346–350Google Scholar
  57. 57.
    Guyton ACJ, Coleman TG, Cawley AW, Manning RD, Norman RA, Ferguson JD (1974) A systems analysis approach to understanding long range arterial blood pressure control and hypertension. Circ Res 35: 159–176Google Scholar
  58. 58.
    Tobian L (1972) A viewpoint concerning the enigma of hypertension. Am J Med 52: 595–609Google Scholar
  59. 59.
    Freis ED (1976) Salt, volume, and prevention of hypertension. Circulation 53: 589–595Google Scholar
  60. 60.
    Birkenhauger WH, deLeeuw PW (1979) Pathophysiological mechanisms in essential hypertension. Pharmacol Ther 8: 297–319Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • R. A. DeFronzo
    • 1
  1. 1.Department of Medicine, Divisions of Endocrine-Metabolism and NephrologyYale University School of MedicineNew HavenUSA

Personalised recommendations