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Aquaporins pp 213-225 | Cite as

Diabetes Insipidus

  • H. A. Jenny LuEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 969)

Abstract

Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. To understand the molecular and cellular mechanisms and pathophysiology of DI and rationales of clinical management of DI is important for both research and clinical practice. This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI ) . This is followed by a discussion of regulatory mechanisms underlying CDI and NDI , with a focus on the regulatory axis of vasopressin, vasopressin receptor 2 (V2R) and the water channel molecule, aquaporin 2 (AQP2 ). The clinical manifestation, diagnosis and management of various forms of DI will also be discussed with highlights of some of the latest therapeutic strategies that are developed from in vitro experiments and animal studies.

Keywords

Diabetes insipidus Nephrogenic diabetes insipidus Aquaporin 2 V2R 

References

  1. 1.
    Nashold BS Jr, Mannarino EM, Robinson RR (1963) Effect of posterior pituitary polypeptides on the flow of urine after injection in lateral ventricle of the brain of a cat. Nature 197:293CrossRefPubMedGoogle Scholar
  2. 2.
    Zimmerman EA, Robinson AG (1976) Hypothalamic neurons secreting vasopressin and neurophysin. Kidney Int 10:12–24CrossRefPubMedGoogle Scholar
  3. 3.
    Hasler U, Nunes P, Bouley R, Lu HA, Matsuzaki T, Brown D (2008) Acute hypertonicity alters aquaporin-2 trafficking and induces a MAPK-dependent accumulation at the plasma membrane of renal epithelial cells. J Biol Chem 283:26643–26661CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Robinson AG (1985) Disorders of antidiuretic hormone secretion. Clin Endocrinol Metab 14:55–88CrossRefPubMedGoogle Scholar
  5. 5.
    Robinson AG, Roberts MM, Evron WA, Verbalis JG, Sherman TG (1990) Hyponatremia in rats induces downregulation of vasopressin synthesis. J Clin Invest 86:1023–1029CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Robinson AG, Fitzsimmons MD (1993) Vasopressin homeostasis: coordination of synthesis, storage and release. Regul Pept 45:225–230CrossRefPubMedGoogle Scholar
  7. 7.
    Fitzsimmons MD, Roberts MM, Robinson AG (1994) Control of posterior pituitary vasopressin content: implications for the regulation of the vasopressin gene. Endocrinology 134:1874–1878PubMedGoogle Scholar
  8. 8.
    Robertson GL, Shelton RL, Athar S (1976) The osmoregulation of vasopressin. Kidney Int 10:25–37CrossRefPubMedGoogle Scholar
  9. 9.
    Horn AM, Robinson IC, Fink G (1985) Oxytocin and vasopressin in rat hypophysial portal blood: experimental studies in normal and Brattleboro rats. J Endocrinol 104:211–224CrossRefPubMedGoogle Scholar
  10. 10.
    Verbalis JG, Baldwin EF, Robinson AG (1986) Osmotic regulation of plasma vasopressin and oxytocin after sustained hyponatremia. Am J Phys 250:R444–R451Google Scholar
  11. 11.
    Murphy D, Waller S, Fairhall K, Carter DA, Robinson CA (1998) Regulation of the synthesis and secretion of vasopressin. Prog Brain Res 119:137–143CrossRefPubMedGoogle Scholar
  12. 12.
    Williams TD, Edwards A, Fairhall KM, Robinson IC, McGarrick GM, Lightman SL (1985) Influence of endogenous and exogenous oestrogens on posterior pituitary secretion in women. Clin Endocrinol 22:589–596CrossRefGoogle Scholar
  13. 13.
    Robertson GL, Athar S (1976) The interaction of blood osmolality and blood volume in regulating plasma vasopressin in man. J Clin Endocrinol Metab 42:613–620CrossRefPubMedGoogle Scholar
  14. 14.
    Dunn FL, Brennan TJ, Nelson AE, Robertson GL (1973) The role of blood osmolality and volume in regulating vasopressin secretion in the rat. J Clin Invest 52:3212–3219CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Schrier RW (1988) Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis, and pregnancy (1). N Engl J Med 319:1065–1072CrossRefPubMedGoogle Scholar
  16. 16.
    Mohring J, Schoun J, Kintz J, Robinson IC, McNeill JR (1983) Vasopressin and oxytocin content are decreased in the brain stems of spontaneously hypertensive rats. Neuroendocrinology 36:457–461CrossRefPubMedGoogle Scholar
  17. 17.
    Padfield PL, Brown JJ, Lever AF, Morton JJ, Robertson JI (1976) Changes of vasopressin in hypertension: cause or effect? Lancet 1:1255–1257CrossRefPubMedGoogle Scholar
  18. 18.
    Cosby RL, Sophocles AM, Durr JA, Perrinjaquet CL, Yee B, Schrier RW (1988) Elevated plasma atrial natriuretic factor and vasopressin in high-altitude pulmonary edema. Ann Intern Med 109:796–799CrossRefPubMedGoogle Scholar
  19. 19.
    Ford SM Jr, Lumpkin HL 3rd (1986) Transient vasopressin-resistant diabetes insipidus of pregnancy. Obstet Gynecol 68:726–728Google Scholar
  20. 20.
    Gordge MP, Williams DJ, Huggett NJ, Payne NN, Neild GH (1995) Loss of biological activity of arginine vasopressin during its degradation by vasopressinase from pregnancy serum. Clin Endocrinol 42:51–58CrossRefGoogle Scholar
  21. 21.
    El-Hennawy AS, Bassi T, Koradia N, Bocirnea A (2003) Transient gestational diabetes insipidus: report of two cases and review of pathophysiology and treatment. J Matern Fetal Neonatal Med 14:349–352CrossRefPubMedGoogle Scholar
  22. 22.
    Davison JM, Sheills EA, Barron WM, Robinson AG, Lindheimer MD (1989) Changes in the metabolic clearance of vasopressin and in plasma vasopressinase throughout human pregnancy. J Clin Invest 83:1313–1318CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Briet JW (1998) Diabetes insipidus, Sheehan’s syndrome and pregnancy. Eur J Obstet Gynecol Reprod Biol 77:201–203CrossRefPubMedGoogle Scholar
  24. 24.
    Woelk JL, Dombroski RA, Brezina PR (2010) Gestational diabetes insipidus, HELLP syndrome and eclampsia in a twin pregnancy: a case report. J Perinatol 30:144–145CrossRefPubMedGoogle Scholar
  25. 25.
    Kennedy S, Hall PM, Seymour AE, Hague WM (1994) Transient diabetes insipidus and acute fatty liver of pregnancy. Br J Obstet Gynaecol 101:387–391CrossRefPubMedGoogle Scholar
  26. 26.
    Aleksandrov N, Audibert F, Bedard MJ, Mahone M, Goffinet F, Kadoch IJ (2010) Gestational diabetes insipidus: a review of an underdiagnosed condition. J Obstet Gynaecol Can 32:225–231CrossRefPubMedGoogle Scholar
  27. 27.
    Burrow GN, Wassenaar W, Robertson GL, Sehl H (1981) DDAVP treatment of diabetes insipidus during pregnancy and the post-partum period. Acta Endocrinol 97:23–25PubMedGoogle Scholar
  28. 28.
    Bichet DG (2006) Nephrogenic diabetes insipidus. Adv Chronic Kidney Dis 13:96–104CrossRefPubMedGoogle Scholar
  29. 29.
    Deen PM, Knoers NV (1998) Vasopressin type-2 receptor and aquaporin-2 water channel mutants in nephrogenic diabetes insipidus. Am J Med Sci 316:300–309CrossRefPubMedGoogle Scholar
  30. 30.
    van den Ouweland AM, Dreesen JC, Verdijk M, Knoers NV, Monnens LA, Rocchi M, van Oost BA (1992) Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus. Nat Genet 2:99–102CrossRefPubMedGoogle Scholar
  31. 31.
    Birnbaumer M (1999) Vasopressin receptor mutations and nephrogenic diabetes insipidus. Arch Med Res 30:465–474CrossRefPubMedGoogle Scholar
  32. 32.
    Bichet DG (2009) V2R mutations and nephrogenic diabetes insipidus. Prog Mol Biol Transl Sci 89:15–29CrossRefPubMedGoogle Scholar
  33. 33.
    Ala Y, Morin D, Mouillac B, Sabatier N, Vargas R, Cotte N, Dechaux M, Antignac C, Arthus MF, Lonergan M, Turner MS, Balestre MN, Alonso G, Hibert M, Barberis C, Hendy GN, Bichet DG, Jard S (1998) Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype. J Am Soc Nephrol 9:1861–1872PubMedGoogle Scholar
  34. 34.
    Sasaki S, Chiga M, Kikuchi E, Rai T, Uchida S (2013) Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2. Clin Exp Nephrol 17:338–344CrossRefPubMedGoogle Scholar
  35. 35.
    Moeller HB, Rittig S, Fenton RA (2013) Nephrogenic diabetes insipidus: essential insights into the molecular background and potential therapies for treatment. Endocr Rev 34:278–301CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Bichet DG, Bockenhauer D (2016) Genetic forms of nephrogenic diabetes insipidus (NDI): vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant). Best Pract Res Clin Endocrinol Metab 30:263–276CrossRefPubMedGoogle Scholar
  37. 37.
    Nejsum LN, Christensen TM, Robben JH, Milligan G, Deen PM, Bichet DG, Levin K (2011) Novel mutation in the AVPR2 gene in a Danish male with nephrogenic diabetes insipidus caused by ER retention and subsequent lysosomal degradation of the mutant receptor. NDT Plus 4:158–163PubMedPubMedCentralGoogle Scholar
  38. 38.
    Tajima T, Okuhara K, Satoh K, Nakae J, Fujieda K (2003) Two novel aquaporin-2 mutations in a sporadic Japanese patient with autosomal recessive nephrogenic diabetes insipidus. Endocr J 50:473–476CrossRefPubMedGoogle Scholar
  39. 39.
    van Lieburg AF, Verdijk MA, Knoers VV, van Essen AJ, Proesmans W, Mallmann R, Monnens LA, van Oost BA, van Os CH, Deen PM (1994) Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene. Am J Hum Genet 55:648–652PubMedPubMedCentralGoogle Scholar
  40. 40.
    Deen PM, Croes H, van Aubel RA, Ginsel LA, van Os CH (1995) Water channels encoded by mutant aquaporin-2 genes in nephrogenic diabetes insipidus are impaired in their cellular routing. J Clin Invest 95:2291–2296CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Werten PJ, Hasler L, Koenderink JB, Klaassen CH, de Grip WJ, Engel A, Deen PM (2001) Large-scale purification of functional recombinant human aquaporin-2. FEBS Lett 504:200–205CrossRefPubMedGoogle Scholar
  42. 42.
    Fujiwara TM, Bichet DG (2005) Molecular biology of hereditary diabetes insipidus. J Am Soc Nephrol 16:2836–2846CrossRefPubMedGoogle Scholar
  43. 43.
    Nielsen S, Frokiaer J, Marples D, Kwon TH, Agre P, Knepper MA (2002) Aquaporins in the kidney: from molecules to medicine. Physiol Rev 82:205–244CrossRefPubMedGoogle Scholar
  44. 44.
    Sasaki S (2004) Nephrogenic diabetes insipidus: update of genetic and clinical aspects. Nephrol Dial Transplant 19:1351–1353CrossRefPubMedGoogle Scholar
  45. 45.
    Mulders SM, Bichet DG, Rijss JP, Kamsteeg EJ, Arthus MF, Lonergan M, Fujiwara M, Morgan K, Leijendekker R, van der Sluijs P, van Os CH, Deen PM (1998) An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex. J Clin Invest 102:57–66CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Bichet DG, El Tarazi A, Matar J, Lussier Y, Arthus MF, Lonergan M, Bockenhauer D, Bissonnette P (2012) Aquaporin-2: new mutations responsible for autosomal-recessive nephrogenic diabetes insipidus-update and epidemiology. Clin Kidney J 5:195–202CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Knoers NV, Deen PM (2001) Molecular and cellular defects in nephrogenic diabetes insipidus. Pediatr Nephrol 16:1146–1152CrossRefPubMedGoogle Scholar
  48. 48.
    Asai T, Kuwahara M, Kurihara H, Sakai T, Terada Y, Marumo F, Sasaki S (2003) Pathogenesis of nephrogenic diabetes insipidus by aquaporin-2 C-terminus mutations. Kidney Int 64:2–10CrossRefPubMedGoogle Scholar
  49. 49.
    Marr N, Bichet DG, Hoefs S, Savelkoul PJ, Konings IB, De Mattia F, Graat MP, Arthus MF, Lonergan M, Fujiwara TM, Knoers NV, Landau D, Balfe WJ, Oksche A, Rosenthal W, Muller D, Van Os CH, Deen PM (2002) Cell-biologic and functional analyses of five new Aquaporin-2 missense mutations that cause recessive nephrogenic diabetes insipidus. J Am Soc Nephrol 13:2267–2277CrossRefPubMedGoogle Scholar
  50. 50.
    Kamsteeg EJ, Savelkoul PJ, Hendriks G, Konings IB, Nivillac NM, Lagendijk AK, van der Sluijs P, Deen PM (2008) Missorting of the Aquaporin-2 mutant E258K to multivesicular bodies/lysosomes in dominant NDI is associated with its monoubiquitination and increased phosphorylation by PKC but is due to the loss of E258. Pflugers Arch 455:1041–1054CrossRefPubMedGoogle Scholar
  51. 51.
    Deen PM, van Balkom BW, Kamsteeg EJ (2000) Routing of the aquaporin-2 water channel in health and disease. Eur J Cell Biol 79:523–530CrossRefPubMedGoogle Scholar
  52. 52.
    Kamsteeg EJ, Deen PM, van Os CH (2000) Defective processing and trafficking of water channels in nephrogenic diabetes insipidus. Exp Nephrol 8:326–331CrossRefPubMedGoogle Scholar
  53. 53.
    McDill BW, Li SZ, Kovach PA, Ding L, Chen F (2006) Congenital progressive hydronephrosis (cph) is caused by an S256 L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation. Proc Natl Acad Sci U S A 103:6952–6957CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Shida Y, Matsuoka H, Chiga M, Uchida S, Sasaki S, Sugihara S (2013) Characterization of AQP-2 gene mutation (R254Q) in a family with dominant nephrogenic DI. Pediatr Int 55:105–107CrossRefPubMedGoogle Scholar
  55. 55.
    Kuwahara M, Iwai K, Ooeda T, Igarashi T, Ogawa E, Katsushima Y, Shinbo I, Uchida S, Terada Y, Arthus MF, Lonergan M, Fujiwara TM, Bichet DG, Marumo F, Sasaki S (2001) Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus. Am J Hum Genet 69:738–748CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Marples D, Christensen S, Christensen EI, Ottosen PD, Nielsen S (1995) Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla. J Clin Invest 95:1838–1845CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Marples D, Frokiaer J, Knepper MA, Nielsen S (1998) Disordered water channel expression and distribution in acquired nephrogenic diabetes insipidus. Proc Assoc Am Physicians 110:401–406PubMedGoogle Scholar
  58. 58.
    Webb RK, Woodhall PB, Tisher CC, Robinson RR (1975) Acute effects of lithium on the renal concentrating mechanism in a primate. Am J Phys 228:909–914Google Scholar
  59. 59.
    Sasaki S, Fushimi K, Saito H, Saito F, Uchida S, Ishibashi K, Kuwahara M, Ikeuchi T, Inui K, Nakajima K et al (1994) Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct. J Clin Invest 93:1250–1256CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Brown D (2003) The ins and outs of aquaporin-2 trafficking. Am J Physiol Ren Physiol 284:F893–F901CrossRefGoogle Scholar
  61. 61.
    Lu H, Sun TX, Bouley R, Blackburn K, McLaughlin M, Brown D (2004) Inhibition of endocytosis causes phosphorylation (S256)-independent plasma membrane accumulation of AQP2. Am J Physiol Ren Physiol 286:F233–F243CrossRefGoogle Scholar
  62. 62.
    Sun TX, Van Hoek A, Huang Y, Bouley R, McLaughlin M, Brown D (2002) Aquaporin-2 localization in clathrin-coated pits: inhibition of endocytosis by dominant-negative dynamin. Am J Physiol Ren Physiol 282:F998–1011CrossRefGoogle Scholar
  63. 63.
    Rice WL, Zhang Y, Chen Y, Matsuzaki T, Brown D, Lu HA (2012) Differential, phosphorylation dependent trafficking of AQP2 in LLC-PK1 cells. PLoS One 7:e32843CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Bouley R, Hasler U, Lu HA, Nunes P, Brown D (2008) Bypassing vasopressin receptor signaling pathways in nephrogenic diabetes insipidus. Semin Nephrol 28:266–278CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Brown D, Bouley R, Paunescu TG, Breton S, Lu HA (2012) New insights into the dynamic regulation of water and acid-base balance by renal epithelial cells. Am J Phys Cell Phys 302:C1421–C1433CrossRefGoogle Scholar
  66. 66.
    Liu SY, Tung YC, Lee CT, Liu HM, Peng SF, Wu MZ, Kuo MF, Tsai WY (2013) Clinical characteristics of central diabetes insipidus in Taiwanese children. J Formos Med Assoc 112:616–620CrossRefPubMedGoogle Scholar
  67. 67.
    Alharfi IM, Stewart TC, Kelly SH, Morrison GC, Fraser DD (2013) Hypernatremia is associated with increased risk of mortality in pediatric severe traumatic brain injury. J Neurotrauma 30:361–366CrossRefPubMedGoogle Scholar
  68. 68.
    Bichet DG (2012) Physiopathology of hereditary polyuric states: a molecular view of renal function. Swiss Med Wkly 142:w13613PubMedGoogle Scholar
  69. 69.
    Robertson GL (2016) Diabetes insipidus: differential diagnosis and management. Best Pract Res Clin Endocrinol Metab 30:205–218CrossRefPubMedGoogle Scholar
  70. 70.
    Dunn AL, Powers JR, Ribeiro MJ, Rickles FR, Abshire TC (2000) Adverse events during use of intranasal desmopressin acetate for haemophilia A and von Willebrand disease: a case report and review of 40 patients. Haemophilia 6:11–14CrossRefPubMedGoogle Scholar
  71. 71.
    Robinson AG (1976) DDAVP in the treatment of central diabetes insipidus. N Engl J Med 294:507–511CrossRefPubMedGoogle Scholar
  72. 72.
    Oiso Y, Robertson GL, Norgaard JP, Juul KV (2013) Clinical review: treatment of neurohypophyseal diabetes insipidus. J Clin Endocrinol Metab 98:3958–3967CrossRefPubMedGoogle Scholar
  73. 73.
    Verrua E, Mantovani G, Ferrante E, Noto A, Sala E, Malchiodi E, Iapichino G, Peccoz PB, Spada A (2013) Severe water intoxication secondary to the concomitant intake of non-steroidal anti-inflammatory drugs and desmopressin: a case report and review of the literature. Hormones (Athens) 12:135–141Google Scholar
  74. 74.
    Bedford JJ, Weggery S, Ellis G, McDonald FJ, Joyce PR, Leader JP, Walker RJ (2008) Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. Clin J Am Soc Nephrol 3:1324–1331CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Dunn MJ, Scharschmidt L, Zambraski E (1984) Mechanisms of the nephrotoxicity of non-steroidal anti-inflammatory drugs. Arch Toxicol Suppl 7:328–337CrossRefPubMedGoogle Scholar
  76. 76.
    Dunn MJ (1984) Nonsteroidal antiinflammatory drugs and renal function. Annu Rev Med 35:411–428CrossRefPubMedGoogle Scholar
  77. 77.
    Kim RJ, Malattia C, Allen M, Moshang T Jr, Maghnie M (2004) Vasopressin and desmopressin in central diabetes insipidus: adverse effects and clinical considerations. Pediatr Endocrinol Rev 2(Suppl 1):115–123PubMedGoogle Scholar
  78. 78.
    Sands JM, Klein JD (2016) Physiological insights into novel therapies for nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 311:F1149–F1152, ajprenal 00418 02016Google Scholar
  79. 79.
    Brown D, Lu HA (2013) Aquaporin-2 inhibitors: fishing in the chemical pool. J Am Soc Nephrol 24:685–686CrossRefPubMedGoogle Scholar
  80. 80.
    Nomura N, Nunes P, Bouley R, Nair AV, Shaw S, Ueda E, Pathomthongtaweechai N, Lu HA, Brown D (2014) High-throughput chemical screening identifies AG-490 as a stimulator of aquaporin 2 membrane expression and urine concentration. Am J Phys Cell Phys 307:C597–C605CrossRefGoogle Scholar
  81. 81.
    Li W, Zhang Y, Bouley R, Chen Y, Matsuzaki T, Nunes P, Hasler U, Brown D, Lu HA (2011) Simvastatin enhances aquaporin-2 surface expression and urinary concentration in vasopressin-deficient Brattleboro rats through modulation of Rho GTPase. Am J Physiol Ren Physiol 301:F309–F318CrossRefGoogle Scholar
  82. 82.
    Bouley R, Lu HA, Nunes P, Da Silva N, McLaughlin M, Chen Y, Brown D (2011) Calcitonin has a vasopressin-like effect on aquaporin-2 trafficking and urinary concentration. J Am Soc Nephrol 22:59–72CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Olesen ET, Rutzler MR, Moeller HB, Praetorius HA, Fenton RA (2011) Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus. Proc Natl Acad Sci U S A 108:12949–12954CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Bouley R, Pastor-Soler N, Cohen O, McLaughlin M, Breton S, Brown D (2005) Stimulation of AQP2 membrane insertion in renal epithelial cells in vitro and in vivo by the cGMP phosphodiesterase inhibitor sildenafil citrate (Viagra). Am J Physiol Ren Physiol 288:F1103–F1112CrossRefGoogle Scholar
  85. 85.
    Sanches TR, Volpini RA, Massola Shimizu MH, Braganca AC, Oshiro-Monreal F, Seguro AC, Andrade L (2012) Sildenafil reduces polyuria in rats with lithium-induced NDI. Am J Physiol Ren Physiol 302:F216–F225CrossRefGoogle Scholar
  86. 86.
    Assadi F, Sharbaf FG (2015) Sildenafil for the treatment of congenital nephrogenic diabetes insipidus. Am J Nephrol 42:65–69CrossRefPubMedGoogle Scholar
  87. 87.
    Procino G, Barbieri C, Carmosino M, Tamma G, Milano S, De Benedictis L, Mola MG, Lazo-Fernandez Y, Valenti G, Svelto M (2011) Fluvastatin modulates renal water reabsorption in vivo through increased AQP2 availability at the apical plasma membrane of collecting duct cells. Pflugers Arch 462:753–766CrossRefPubMedGoogle Scholar
  88. 88.
    Li JH, Chou CL, Li B, Gavrilova O, Eisner C, Schnermann J, Anderson SA, Deng CX, Knepper MA, Wess J (2009) A selective EP4 PGE2 receptor agonist alleviates disease in a new mouse model of X-linked nephrogenic diabetes insipidus. J Clin Invest 119:3115–3126CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Olesen ET, Moeller HB, Assentoft M, MacAulay N, Fenton RA (2015) The vasopressin type-2 receptor and prostaglandin receptors EP2 and EP4 can increase aquaporin-2 plasma membrane targeting through a cAMP independent pathway. Am J Physiol Renal Physiol, ajprenal 00559 02015Google Scholar
  90. 90.
    Efe O, Klein JD, LaRocque LM, Ren H, Sands JM (2016) Metformin improves urine concentration in rodents with nephrogenic diabetes insipidus. JCI Insight 1:e88409Google Scholar
  91. 91.
    Yang B, Zhao D, Verkman AS (2008) Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock-in mouse model of aquaporin-2 mutation. FASEB J 23:503–512CrossRefPubMedGoogle Scholar
  92. 92.
    Cheung PW, Nomura N, Nair AV, Pathomthongtaweechai N, Ueberdiek L, Jenny Lu HA, Brown D, Bouley R (2016) EGF receptor inhibition by erlotinib increases aquaporin 2-,mediated renal water reabsorption. J Am Soc Nephrol 27(10):3105–3116Google Scholar

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© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  1. 1.Program in Membrane Biology, Division of NephrologyMassachusetts General Hospital and Harvard Medical SchoolBostonUSA

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