RAS and sex differences in diabetic nephropathy

American Journal of Physiology - Renal Physiology

Volumn 310, Issue 10, 2016, Pages F945-F957

  Clotet, Sergi ^a   Riera, Marta ^a   Pascual, Julio ^a   Soler, María José ^a  

^a HOSPITAL DEL MAR   (Spain)

Author keywords

Angiotensin converting enzyme; Angiotensin converting enzyme 2; Gender

Indexed keywords

ANDROGEN; ANGIOTENSIN CONVERTING ENZYME 2; ANGIOTENSINOGEN; DIPEPTIDYL CARBOXYPEPTIDASE; ESTROGEN; ORAL CONTRACEPTIVE AGENT; RENIN; SEX HORMONE;

ANDROGEN THERAPY; CARDIOVASCULAR FUNCTION; DIABETIC NEPHROPATHY; DISEASE COURSE; ENZYME LOCALIZATION; ESTROGEN THERAPY; EXPERIMENTAL DIABETES MELLITUS; EXPERIMENTAL STUDY; FEMALE; HUMAN; INCIDENCE; INSULIN DEPENDENT DIABETES MELLITUS; KIDNEY FUNCTION; MALE; META ANALYSIS (TOPIC); NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SEX DIFFERENCE; SYSTEMATIC REVIEW (TOPIC);

EID: 84980614145     PISSN: 1931857X     EISSN: 15221466     Source Type: Journal    
DOI: 10.1152/ajprenal.00292.2015     Document Type: Review

References (144)

1. Aaronson DS, Muller M, Neves SR, Chung WC, Jayaram G, Iyengar R, Ram PT. An androgen-IL-6-Stat3 autocrine loop re-routes EGF signal in prostate cancer cells. Mol Cell Endocrinol 270: 50-56, 2007
2. Abbate R, Mannucci E, Cioni G, Fatini C, Marcucci R. Diabetes and sex: from pathophysiology to personalized medicine. Intern Emerg Med 7, Suppl 3: S215-S219, 2012
3. Ahmed SB, Hovind P, Parving HH, Rossing P, Price DA, Laffel LM, Lansang MC, Stevanovic R, Fisher ND, Hollenberg NK. Oral contraceptives, angiotensin-dependent renal vasoconstriction, and risk of diabetic nephropathy. Diabetes Care 28: 1988-1994, 2005
4. American Diabetes Association. Standards of medical care in diabetes-2011. Diabetes Care 34, Suppl 1: S11-S61, 2011
5. Amin R, Schultz C, Ong K, Frystyk J, Dalton RN, Perry L, Orskov H, Dunger DB, Oxford Regional Prospective Study. Low IGF-I and elevated testosterone during puberty in subjects with type 1 diabetes developing microalbuminuria compared with normoalbuminuric control subjects: the Oxford Regional Prospective Study. Diabetes Care 26: 1456-1461, 2003
6. Anderson S, Chapman JG, Oyama TT, Komers R. Effect of orchiectomy on renal function in control and diabetic rats with chronic inhibition of nitric oxide. Clin Exp Pharmacol Physiol 37: 19-23, 2010
7. Anguiano L, Riera M, Pascual J, Valdivielso JM, Barrios C, Betriu A, Mojal S, Fernandez E, Soler MJ, Investigators from the NEFRONA Study. Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease. Nephrol Dial Transplant 30: 1176-1185, 2015
8. Barrett-Connor E. Gender differences and disparities in all-cause and coronary heart disease mortality: epidemiological aspects. Best Pract Res Clin Endocrinol Metab 27: 481-500, 2013
9. Border WA, Noble NA. Interactions of transforming growth factor-beta and angiotensin II in renal fibrosis. Hypertension 31: 181-188, 1998
10. Brand JS, Wareham NJ, Dowsett M, Folkerd E, van der Schouw YT, Luben RN, Khaw KT. Associations of endogenous testosterone and SHBG with glycated haemoglobin in middle-aged and older men. Clin Endocrinol (Oxf) 74: 572-578, 2011
11. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S, Investigators RS. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345: 861-869, 2001
12. Brewster UC, Perazella MA. The renin-angiotensin-aldosterone system and the kidney: effects on kidney disease. Am J Med 116: 263-272, 2004
13. Brezniceanu ML, Liu F, Wei CC, Tran S, Sachetelli S, Zhang SL, Guo DF, Filep JG, Ingelfinger JR, Chan JS. Catalase overexpression attenuates angiotensinogen expression and apoptosis in diabetic mice. Kidney Int 71: 912-923, 2007
14. Castoldi G, di Gioia CR, Bombardi C, Maestroni S, Carletti R, Steckelings UM, Dahlof B, Unger T, Zerbini G, Stella A. Prevention of diabetic nephropathy by compound 21, selective agonist of angiotensin type 2 receptors, in Zucker diabetic fatty rats. Am J Physiol Renal Physiol 307: F1123-F1131, 2014
15. Catanuto P, Doublier S, Lupia E, Fornoni A, Berho M, Karl M, Striker GE, Xia X, Elliot S. 17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes. Kidney Int 75: 1194-1201, 2009
16. Chandel A, Dhindsa S, Topiwala S, Chaudhuri A, Dandona P. Testosterone concentration in young patients with diabetes. Diabetes Care 31: 2013-2017, 2008
17. Chen JQ, Cammarata PR, Baines CP, Yager JD. Regulation of mitochondrial respiratory chain biogenesis by estrogens/estrogen receptors and physiological, pathological and pharmacological implications. Biochim Biophys Acta 1793: 1540-1570, 2009
18. Cherney DZ, Sochett EB, Miller JA. Gender differences in renal responses to hyperglycemia and angiotensin-converting enzyme inhibi
19. Chin M, Isono M, Isshiki K, Araki S, Sugimoto T, Guo B, Sato H, Haneda M, Kashiwagi A, Koya D. Estrogen and raloxifene, a selective estrogen receptor modulator, ameliorate renal damage in db/db mice. Am J Pathol 166: 1629-1636, 2005
20. Cohen AM, Rosenmann E. Male sex hormone and nephropathy in Cohen diabetic rat (Genetically selected sucrose fed). Diabete Metab 10: 199-205, 1984
21. Collins AJ, Foley RN, Chavers B, Gilbertson D, Herzog C, Ishani A, Johansen K, Kasiske BL, Kutner N, Liu J, St Peter W, Guo H, Hu Y, Kats A, Li S, Li S, Maloney J, Roberts T, Skeans M, Snyder J, Solid C, Thompson B, Weinhandl E, Xiong H, Yusuf A, Zaun D, Arko C, Chen SC, Daniels F, Ebben J, Frazier E, Johnson R, Sheets D, Wang X, Forrest B, Berrini D, Constantini E, Everson S, Eggers P, Agodoa L. US Renal Data System 2013 Annual Data Report. Am J Kidney Dis 63: A7, 2014
22. Cunningham GR, Stephens-Shields AJ, Rosen RC, Wang C, Ellenberg SS, Matsumoto AM, Bhasin S, Molitch ME, Farrar JT, Cella D, Barrett-Connor E, Cauley JA, Cifelli D, Crandall JP, Ensrud KE, Fluharty L, Gill TM, Lewis CE, Pahor M, Resnick SM, Storer TW, Swerdloff RS, Anton S, Basaria S, Diem S, Tabatabaie V, Hou X, Snyder PJ. Association of sex hormones with sexual function, vitality, and physical function of symptomatic older men with low testosterone levels at baseline in the testosterone trials. J Clin Endocrinol Metab 100: 1146-1155, 2015
23. Cvetkovic TP, Stefanovic NZ, Velickovic-Radovanovic RM, Paunovic GJ, Djordjevic VM, Stojanovic DR, Stojanovic IR, Pavlovic DD. Gender differences in oxidative and nitrosative stress parameters in kidney transplant patients on tacrolimus-based immunosuppression. Int Urol Nephrol 46: 1217-1224, 2014
24. De Alencar Franco Costa D, Todiras M, Campos LA, Cipolla-Neto J, Bader M, Baltatu OC. Sex-dependent differences in renal angiotensinogen as an early marker of diabetic nephropathy. Acta Physiol (Oxf) 213: 740-746, 2015
25. Diamond-Stanic MK, You YH, Sharma K. Sugar, sex, and TGF-beta in diabetic nephropathy. Semin Nephrol 32: 261-268, 2012
26. Dixon A, Wells CC, Singh S, Babayan R, Maric C. Renoprotective effects of a selective estrogen receptor modulator, raloxifene, in an animal model of diabetic nephropathy. Am J Nephrol 27: 120-128, 2007
27. Dorflinger LJ. Metabolic effects of implantable steroid contraceptives for women. Contraception 65: 47-62, 2002
28. Dorman JS, Steenkiste AR, Foley TP, Strotmeyer ES, Burke JP, Kuller LH, Kwoh CK, Familial A, Diabetes S. Menopause in type 1 diabetic women: is it premature? Diabetes 50: 1857-1862, 2001
29. Doublier S, Lupia E, Catanuto P, Periera-Simon S, Xia X, Korach K, Berho M, Elliot SJ, Karl M. Testosterone and 17beta-estradiol have opposite effects on podocyte apoptosis that precedes glomerulosclerosis in female estrogen receptor knockout mice. Kidney Int 79: 404-413, 2011
30. Elliot SJ, Berho M, Korach K, Doublier S, Lupia E, Striker GE, Karl M. Gender-specific effects of endogenous testosterone: female alphaestrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis. Kidney Int 72: 464-472, 2007
31. Elliot SJ, Karl M, Berho M, Potier M, Zheng F, Leclercq B, Striker GE, Striker LJ. Estrogen deficiency accelerates progression of glomerulosclerosis in susceptible mice. Am J Pathol 162: 1441-1448, 2003
32. Ferreira NS, Cau SB, Silva MA, Manzato CP, Mestriner FL, Matsumoto T, Carneiro FS, Tostes RC. Diabetes impairs the vascular effects of aldosterone mediated by G protein-coupled estrogen receptor activation. Front Pharmacol 6: 34, 2015
33. Fischer M, Baessler A, Schunkert H. Renin angiotensin system and gender differences in the cardiovascular system. Cardiovasc Res 53: 672-677, 2002
34. Francomano D, Bruzziches R, Barbaro G, Lenzi A, Aversa A. Effects of testosterone undecanoate replacement and withdrawal on cardiometabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study. J Endocrinol Invest 37: 401-411, 2014
35. Fukui M, Soh J, Tanaka M, Kitagawa Y, Hasegawa G, Yoshikawa T, Miki T, Nakamura N. Low serum testosterone concentration in middleaged men with type 2 diabetes. Endocr J 54: 871-877, 2007
36. Gaspard UJ, Lefebvre PJ. Clinical aspects of the relationship between oral contraceptives, abnormalities in carbohydrate metabolism, and the development of cardiovascular disease. Am J Obstet Gynecol 163: 334-343, 1990
37. Gros R, Ding Q, Liu B, Chorazyczewski J, Feldman RD. Aldosterone mediates its rapid effects in vascular endothelial cells through GPER activation. Am J Physiol Cell Physiol 304: C532-C540, 2013
38. Grossmann M, Thomas MC, Panagiotopoulos S, Sharpe K, Macisaac RJ, Clarke S, Zajac JD, Jerums G. Low testosterone levels are common and associated with insulin resistance in men with diabetes. J Clin Endocrinol Metab 93: 1834-1840, 2008
39. Gupte M, Thatcher SE, Boustany-Kari CM, Shoemaker R, Yiannikouris F, Zhang X, Karounos M, Cassis LA. Angiotensin converting enzyme 2 contributes to sex differences in the development of obesity hypertension in C57BL/6 mice. Arterioscler Thromb Vasc Biol 32: 1392-1399, 2012
40. Hadjadj S, Gourdy P, Zaoui P, Guerci B, Roudaut N, Gautier JF, Chabin M, Mauco G, Ragot S, Group RS. Effect of raloxifene-a selective oestrogen receptor modulatoron kidney function in postmenopausal women with Type 2 diabetes: results from a randomized, placebo-controlled pilot trial. Diabet Med 24: 906-910, 2007
41. Haffner SM, Shaten J, Stern MP, Smith GD, Kuller L. Low levels of sex hormone-binding globulin and testosterone predict the development of non-insulin-dependent diabetes mellitus in men. MRFIT Research Group Multiple Risk Factor Intervention Trial. Am J Epidemiol 143: 889-897, 1996
42. Hartono SP, Knudsen BE, Lerman LO, Textor SC, Grande JP. Combined effect of hyperfiltration and renin angiotensin system activation on development of chronic kidney disease in diabetic db/db mice. BMC Nephrol 15: 58, 2014
43. Harvengt C. Effect of oral contraceptive use on the incidence of impaired glucose tolerance and diabetes mellitus. Diabete Metab 18: 71-77, 1992
44. Hilliard LM, Chow CL, Mirabito KM, Steckelings UM, Unger T, Widdop RE, Denton KM. Angiotensin type 2 receptor stimulation increases renal function in female, but not male, spontaneously hypertensive rats. Hypertension 64: 378-383, 2014
45. Holt SK, Lopushnyan N, Hotaling J, Sarma AV, Dunn RL, Cleary PA, Braffett BH, Gatcomb P, Martin C, Herman WH, Wessells H, Diabetes C, Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Prevalence of low testosterone and predisposing risk factors in men with type 1 diabetes mellitus: findings from the DCCT/EDIC. J Clin Endocrinol Metab 99: E1655-E1660, 2014
46. Hsieh TJ, Zhang SL, Filep JG, Tang SS, Ingelfinger JR, Chan JS. High glucose stimulates angiotensinogen gene expression via reactive oxygen species generation in rat kidney proximal tubular cells. Endocrinology 143: 2975-2985, 2002
47. Jones CA, Krolewski AS, Rogus J, Xue JL, Collins A, Warram JH. Epidemic of end-stage renal disease in people with diabetes in the United States population: do we know the cause? Kidney Int 67: 1684-1691, 2005
48. Kamiyama M, Urushihara M, Morikawa T, Konishi Y, Imanishi M, Nishiyama A, Kobori H. Oxidative stress/angiotensinogen/renin-angiotensin system axis in patients with diabetic nephropathy. Int J Mol Sci 14: 23045-23062, 2013
49. Keane WF, Brenner BM, de Zeeuw D, Grunfeld JP, McGill J, Mitch WE, Ribeiro AB, Shahinfar S, Simpson RL, Snapinn SM, Toto R, Investigators RS. The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Kidney Int 63: 1499-1507, 2003
50. Keck M, Romero-Aleshire MJ, Cai Q, Hoyer PB, Brooks HL. Hormonal status affects the progression of STZ-induced diabetes and diabetic renal damage in the VCD mouse model of menopause. Am J Physiol Renal Physiol 293: F193-F199, 2007
51. Kelly DJ, Skinner SL, Gilbert RE, Cox AJ, Cooper ME, WilkinsonBerka JL. Effects of endothelin or angiotensin II receptor blockade on diabetes in the transgenic (mRen-2)27 rat. Kidney Int 57: 1882-1894, 2000
52. Kelsey MM, Bjornstad P, McFann K, Nadeau K. Testosterone concentration and insulin sensitivity in young men with type 1 and type 2 diabetes. Pediatr Diabetes In press
53. Kim KS, Kang SH, Kim MJ, Kim SK, Kim YL, Park WK, Park SW, Cho YW. Low serum testosterone concentrations in hospitalized men with poorly controlled type 2 diabetes. Endocrinol Metab (Seoul) 29: 574-578, 2014
54. Koulis C, Chow BS, McKelvey M, Steckelings UM, Unger T, ThallasBonke V, Thomas MC, Cooper ME, Jandeleit-Dahm KA, Allen TJ. AT2R agonist, compound 21, is reno-protective against type 1 diabetic nephropathy. Hypertension 65: 1073-1081, 2015
55. Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, Salonen R, Salonen JT. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 27: 1036-1041, 2004
56. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I, Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345: 851-860, 2001
57. Lim YK, Retnam L, Bhagavath B, Sethi SK, bin Ali A, Lim SK. Gonadal effects on plasma ACE activity in mice. Atherosclerosis 160: 311-316, 2002
58. Lin HK, Hu YC, Yang L, Altuwaijri S, Chen YT, Kang HY, Chang C. Suppression versus induction of androgen receptor functions by the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer LNCaP cells with different passage numbers. J Biol Chem 278: 50902-50907, 2003
59. Liu J, Ji H, Zheng W, Wu X, Zhu JJ, Arnold AP, Sandberg K. Sex differences in renal angiotensin converting enzyme 2 (ACE2) activity are 17beta-oestradiol-dependent and sex chromosome-independent. Biol Sex Differ 1: 6, 2010
60. Liu X, Shi Q, Sigmund CD. Interleukin-1beta attenuates renin gene expression via a mitogen-activated protein kinase kinase-extracellular signal-regulated kinase and signal transducer and activator of transcription 3-dependent mechanism in As4.1 cells. Endocrinology 147: 6011-6018, 2006
61. Lo CS, Liu F, Shi Y, Maachi H, Chenier I, Godin N, Filep JG, Ingelfinger JR, Zhang SL, Chan JS. Dual RAS blockade normalizes angiotensin-converting enzyme-2 expression and prevents hypertension and tubular apoptosis in Akita angiotensinogen-transgenic mice. Am J Physiol Renal Physiol 302: F840-F852, 2012
62. Lonergan PE, Tindall DJ. Androgen receptor signaling in prostate cancer development and progression. J Carcinog 10: 20, 2011
63. Lovegrove AS, Sun J, Gould KA, Lubahn DB, Korach KS, Lane PH. Estrogen receptor alpha-mediated events promote sex-specific diabetic glomerular hypertrophy. Am J Physiol Renal Physiol 287: F586-F591, 2004
64. Machado RB, Careta MF, Balducci GP, Araujo TS, Bernardes CR. Effects of estrogen therapy on microalbuminuria in healthy post-menopausal women. Gynecol Endocrinol 24: 681-685, 2008
65. Maggio M, Lauretani F, Ceda GP, Bandinelli S, Basaria S, Paolisso G, Giumelli C, Luci M, Najjar SS, Metter EJ, Valenti G, Guralnik J, Ferrucci L. Estradiol and metabolic syndrome in older italian men: The InCHIANTI Study. J Androl 31: 155-162, 2010
66. Manigrasso MB, Sawyer RT, Hutchens ZM Jr. Flynn ER, Maric-Bilkan C. Combined inhibition of aromatase activity and dihydrotestosterone supplementation attenuates renal injury in male streptozotocin (STZ)-induced diabetic rats. Am J Physiol Renal Physiol 302: F1203-F1209, 2012
67. Manigrasso MB, Sawyer RT, Marbury DC, Flynn ER, Maric C. Inhibition of estradiol synthesis attenuates renal injury in male streptozotocin-induced diabetic rats. Am J Physiol Renal Physiol 301: F634-F640, 2011
68. Mankhey RW, Bhatti F, Maric C. 17beta-Estradiol replacement improves renal function and pathology associated with diabetic nephropathy. Am J Physiol Renal Physiol 288: F399-F405, 2005
69. Mankhey RW, Wells CC, Bhatti F, Maric C. 17beta-Estradiol supplementation reduces tubulointerstitial fibrosis by increasing MMP activity in the diabetic kidney. Am J Physiol Regul Integr Comp Physiol 292: R769-R777, 2007
70. Maric C, Forsblom C, Thorn L, Waden J, Groop PH, FinnDiane Study Group. Association between testosterone, estradiol and sex hormone binding globulin levels in men with type 1 diabetes with nephropathy. Steroids 75: 772-778, 2010
71. Maric C, Sandberg K, Hinojosa-Laborde C. Glomerulosclerosis and tubulointerstitial fibrosis are attenuated with 17beta-estradiol in the aging Dahl salt sensitive rat. J Am Soc Nephrol 15: 1546-1556, 2004
72. Maric C, Sullivan S. Estrogens and the diabetic kidney. Gend Med 5, Suppl A: S103-S113, 2008
73. Matavelli LC, Zatz R, Siragy HM. A nonpeptide angiotensin II type 2 receptor agonist prevents renal inflammation in early diabetes. J Cardiovasc Pharmacol 65: 371-376, 2015
74. Matsuda T, Junicho A, Yamamoto T, Kishi H, Korkmaz K, Saatcioglu F, Fuse H, Muraguchi A. Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells. Biochem Biophys Res Commun 283: 179-187, 2001
75. Mauer M, Drummond K. The early natural history of nephropathy in type 1 diabetes. I. Study design and baseline characteristics of the study participants. Diabetes 51: 1572-1579, 2002
76. Miller JA, Cherney DZ, Duncan JA, Lai V, Burns KD, Kennedy CR, Zimpelmann J, Gao W, Cattran DC, Scholey JW. Gender differences in the renal response to renin-angiotensin system blockade. J Am Soc Nephrol 17: 2554-2560, 2006
77. Miyagawa K, Kondo T, Goto R, Matsuyama R, Ono K, Kitano S, Kawasaki S, Igata M, Kawashima J, Matsumura T, Motoshima H, Araki E. Effects of combination therapy with vildagliptin and valsartan in a mouse model of type 2 diabetes. Cardiovasc Diabetol 12: 160, 2013
78. Mizuiri S, Hemmi H, Arita M, Ohashi Y, Tanaka Y, Miyagi M, Sakai K, Ishikawa Y, Shibuya K, Hase H, Aikawa A. Expression of ACE and ACE2 in individuals with diabetic kidney disease and healthy controls. Am J Kidney Dis 51: 613-623, 2008
79. Moskovic DJ, Araujo AB, Lipshultz LI, Khera M. The 20-year public health impact and direct cost of testosterone deficiency in U.S. men. J Sex Med 10: 562-569, 2013
80. Navarro-Casado L, Juncos-Tobarra MA, Chafer-Rudilla M, de Onzono LI, Blazquez-Cabrera JA, Miralles-Garcia JM. Effect of experimental diabetes and STZ on male fertility capacity study in rats. J Androl 31: 584-592, 2010
81. Nedungadi TP, Clegg DJ. Sexual dimorphism in body fat distribution and risk for cardiovascular diseases. J Cardiovasc Transl Res 2: 321-327, 2009
82. Negulescu O, Bognar I, Lei J, Devarajan P, Silbiger S, Neugarten J. Estradiol reverses TGF-beta1-induced mesangial cell apoptosis by a casein kinase 2-dependent mechanism. Kidney Int 62: 1989-1998, 2002
83. Neugarten J. Gender and the progression of renal disease. J Am Soc Nephrol 13: 2807-2809, 2002
84. Neugarten J, Golestaneh L. Gender and the prevalence and progression of renal disease. Adv Chronic Kidney Dis 20: 390-395, 2013
85. Noonan WT, Banks RO. Renal function and glucose transport in male and female mice with diet-induced type II diabetes mellitus. Proc Soc Exp Biol Med 225: 221-230, 2000
86. Orchard TJ, Dorman JS, Maser RE, Becker DJ, Drash AL, Ellis D, LaPorte RE, Kuller LH. Prevalence of complications in IDDM by sex and duration. Pittsburgh Epidemiology of Diabetes Complications Study II. Diabetes 39: 1116-1124, 1990
87. Oudit GY, Herzenberg AM, Kassiri Z, Wong D, Reich H, Khokha R, Crackower MA, Backx PH, Penninger JM, Scholey JW. Loss of angiotensin-converting enzyme-2 leads to the late development of angiotensin II-dependent glomerulosclerosis. Am J Pathol 168: 1808-1820, 2006
88. Oudit GY, Liu GC, Zhong J, Basu R, Chow FL, Zhou J, Loibner H, Janzek E, Schuster M, Penninger JM, Herzenberg AM, Kassiri Z, Scholey JW. Human recombinant ACE2 reduces the progression of diabetic nephropathy. Diabetes 59: 529-538, 2010
89. Pan L, Black TA, Shi Q, Jones CA, Petrovic N, Loudon J, Kane C, Sigmund CD, Gross KW. Critical roles of a cyclic AMP responsive element and an E-box in regulation of mouse renin gene expression. J Biol Chem 276: 45530-45538, 2001
90. Parving HH, Gall MA, Skott P, Jorgensen HE, Lokkegaard H, Jorgensen F, Nielsen B, Larsen S. Prevalence and causes of albuminuria in non-insulin-dependent diabetic patients. Kidney Int 41: 758-762, 1992
91. Patel KL, Mhetras SB, Varthakavi PK, Merchant PC, Nihalani KD. Microalbuminuria in insulin dependent diabetes mellitus. J Assoc Physicians India 47: 589-595, 1999
92. Patinha D, Afonso J, Sousa T, Morato M, Albino-Teixeira A. Diabetes-induced increase of renal medullary hydrogen peroxide and urinary angiotensinogen is similar in normotensive and hypertensive rats. Life Sci 108: 71-79, 2014
93. Pelekanou V, Notas G, Stathopoulos EN, Castanas E, Kampa M. Androgen receptors in early and castration resistant prostate cancer: friend or foe? Hormones (Athens) 12: 224-235, 2013
94. Pendergrass KD, Pirro NT, Westwood BM, Ferrario CM, Brosnihan KB, Chappell MC. Sex differences in circulating and renal angiotensins of hypertensive mRen(2) Lewis but not normotensive Lewis rats. Am J Physiol Heart Circ Physiol 295: H10-H20, 2008
95. Potier M, Karl M, Zheng F, Elliot SJ, Striker GE, Striker LJ. Estrogen-related abnormalities in glomerulosclerosis-prone mice: reduced mesangial cell estrogen receptor expression and prosclerotic response to estrogens. Am J Pathol 160: 1877-1885, 2002
96. Prabhu A, Xu Q, Manigrasso MB, Biswas M, Flynn E, Iliescu R, Lephart ED, Maric C. Expression of aromatase, androgen and estrogen receptors in peripheral target tissues in diabetes. Steroids 75: 779-787, 2010
97. Raile K, Galler A, Hofer S, Herbst A, Dunstheimer D, Busch P, Holl RW. Diabetic nephropathy in 27,805 children, adolescents, and adults with type 1 diabetes: effect of diabetes duration, A1C, hypertension, dyslipidemia, diabetes onset, and sex. Diabetes Care 30: 2523-2528, 2007
98. Ravid M, Brosh D, Ravid-Safran D, Levy Z, Rachmani R. Main risk factors for nephropathy in type 2 diabetes mellitus are plasma cholesterol levels, mean blood pressure, and hyperglycemia. Arch Intern Med 158: 998-1004, 1998
99. Roberts MA, Velkoska E, Ierino FL, Burrell LM. Angiotensinconverting enzyme 2 activity in patients with chronic kidney disease. Nephrol Dial Transplant 28: 2287-2294, 2013
100. Roscioni SS, Heerspink HJ, de Zeeuw D. The effect of RAAS blockade on the progression of diabetic nephropathy. Nat Rev Nephrol 10: 77-87, 2014
101. Rosenmann E, Yanko L, Cohen AM. Female sex hormone and nephropathy in Cohen diabetic rat (genetically selected sucrose-fed). Horm Metab Res 16: 11-16, 1984
102. Ruiz-Ortega M, Ruperez M, Esteban V, Rodriguez-Vita J, SanchezLopez E, Carvajal G, Egido J. Angiotensin II: a key factor in the inflammatory and fibrotic response in kidney diseases. Nephrol Dial Transplant 21: 16-20, 2006
103. Ruster C, Wolf G. Angiotensin II as a morphogenic cytokine stimulating renal fibrogenesis. J Am Soc Nephrol 22: 1189-1199, 2011
104. Saad F, Yassin A, Almehmadi Y, Doros G, Gooren L. Effects of long-term testosterone replacement therapy, with a temporary intermission, on glycemic control of nine hypogonadal men with type 1 diabetes mellitus-a series of case reports. Aging Male 18: 164-168, 2015
105. Saha I, Das J, Maiti B, Chatterji U. A protective role of arecoline hydrobromide in experimentally induced male diabetic rats. Biomed Res Int 2015: 136738, 2015
106. Salonia A, Lanzi R, Scavini M, Pontillo M, Gatti E, Petrella G, Licata G, Nappi RE, Bosi E, Briganti A, Rigatti P, Montorsi F. Sexual function and endocrine profile in fertile women with type 1 diabetes. Diabetes Care 29: 312-316, 2006
107. Savage S, Nagel NJ, Estacio RO, Lukken N, Schrier RW. Clinical factors associated with urinary albumin excretion in type II diabetes. Am J Kidney Dis 25: 836-844, 1995
108. Shufelt CL, Bairey Merz CN. Contraceptive hormone use and cardiovascular disease. J Am Coll Cardiol 53: 221-231, 2009
109. Silbiger S, Lei J, Ziyadeh FN, Neugarten J. Estradiol reverses TGFbeta1-stimulated type IV collagen gene transcription in murine mesangial cells. Am J Physiol Renal Physiol 274: F1113-F1118, 1998
110. Silbiger S, Neugarten J. Gender and human chronic renal disease. Gend Med 5, Suppl A: S3-S10, 2008
111. Slyvka Y, Wang Z, Yee J, Inman SR, Nowak FV. Antioxidant diet, gender and age affect renal expression of nitric oxide synthases in obese diabetic rats. Nitric Oxide 24: 50-60, 2011
112. Soler MJ, Riera M, Crespo M, Mir M, Marquez E, Pascual MJ, Puig JM, Pascual J. Circulating angiotensin-converting enzyme 2 activity in kidney transplantation: a longitudinal pilot study. Nephron Clin Pract 121: c144-c150, 2012
113. Soro-Paavonen A, Gordin D, Forsblom C, Rosengard-Barlund M, Waden J, Thorn L, Sandholm N, Thomas MC, Groop PH. Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications. J Hypertens 30: 375-383, 2012
114. Sowers M, Derby C, Jannausch ML, Torrens JI, Pasternak R. Insulin resistance, hemostatic factors, and hormone interactions in preand perimenopausal women: SWAN. J Clin Endocrinol Metab 88: 4904-4910, 2003
115. Sullivan JC. Sex and the renin-angiotensin system: inequality between the sexes in response to RAS stimulation and inhibition. Am J Physiol Regul Integr Comp Physiol 294: R1220-R1226, 2008
116. Sun J, Devish K, Langer WJ, Carmines PK, Lane PH. Testosterone treatment promotes tubular damage in experimental diabetes in prepubertal rats. Am J Physiol Renal Physiol 292: F1681-F1690, 2007
117. Szekacs B, Vajo Z, Varbiro S, Kakucs R, Vaslaki L, Acs N, Mucsi I, Brinton EA. Postmenopausal hormone replacement improves proteinuria and impaired creatinine clearance in type 2 diabetes mellitus and hypertension. Br J Obstet Gynecol 107: 1017-1021, 2000
118. Taal MW, Brenner BM. Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int 57: 1803-1817, 2000
119. Taylor SR, Meadowcraft LM, Williamson B. Prevalence, pathophysiology, and management of androgen deficiency in men with metabolic syndrome, type 2 diabetes mellitus, or both. Pharmacotherapy 35: 780-792, 2015
120. Tomar R, Dhindsa S, Chaudhuri A, Mohanty P, Garg R, Dandona P. Contrasting testosterone concentrations in type 1 and type 2 diabetes. Diabetes Care 29: 1120-1122, 2006
121. Tomiyoshi Y, Sakemi T, Aoki S, Miyazono M. Different effects of castration and estrogen administration on glomerular injury in spontaneously hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Nephron 92: 860-867, 2002
122. Touyz RM, Schiffrin EL. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev 52: 639-672, 2000
123. Traish AM. Testosterone and weight loss: the evidence. Curr Opin Endocrinol Diabetes Obes 21: 313-322, 2014
124. Troisi RJ, Cowie CC, Harris MI. Oral contraceptive use and glucose metabolism in a national sample of women in the United States. Am J Obstet Gynecol 183: 389-395, 2000
125. Ueda T, Bruchovsky N, Sadar MD. Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways. J Biol Chem 277: 7076-7085, 2002
126. Uzun D, Korkmaz GG, Sitar ME, Cebe T, Yanar K, Cakatay U, Aydin S. Oxidative damage parameters in renal tissues of aged and young rats based on gender. Clin Interv Aging 8: 809-815, 2013
127. Vaucher L, Funaro MG, Mehta A, Mielnik A, Bolyakov A, Prossnitz ER, Schlegel PN, Paduch DA. Activation of GPER-1 estradiol receptor downregulates production of testosterone in isolated rat Leydig cells and adult human testis. PLoS One 9: e92425, 2014
128. Vikan T, Schirmer H, Njolstad I, Svartberg J. Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men. Eur J Endocrinol 162: 747-754, 2010
129. Villar G, Garcia Y, Goicolea I, Vazquez JA. Determinants of development of microalbuminuria in normotensive patients with type 1 and type 2 diabetes. Diabetes Metab 25: 246-254, 1999
130. Weir RJ, Briggs E, Mack A, Naismith L, Taylor L, Wilson E. Blood pressure in women taking oral contraceptives. Br Med J 1: 533-535, 1974
131. Wells CC, Riazi S, Mankhey RW, Bhatti F, Ecelbarger C, Maric C. Diabetic nephropathy is associated with decreased circulating estradiol levels and imbalance in the expression of renal estrogen receptors. Gend Med 2: 227-237, 2005
132. Williams G. Aromatase up-regulation, insulin and raised intracellular oestrogens in men, induce adiposity, metabolic syndrome and prostate disease, via aberrant ER-alpha and GPER signalling. Mol Cell Endocrinol 351: 269-278, 2012
133. Wolf G. Renal injury due to renin-angiotensin-aldosterone system activation of the transforming growth factor-beta pathway. Kidney Int 70: 1914-1919, 2006
134. Wong DW, Oudit GY, Reich H, Kassiri Z, Zhou J, Liu QC, Backx PH, Penninger JM, Herzenberg AM, Scholey JW. Loss of angiotensin-converting enzyme-2 (Ace2) accelerates diabetic kidney injury. Am J Pathol 171: 438-451, 2007
135. Wynn V, Doar JW. Some effects of oral contraceptives on carbohydrate metabolism. Lancet 2: 761-765, 1969
136. Wysocki J, Ye M, Soler MJ, Gurley SB, Xiao HD, Bernstein KE, Coffman TM, Chen S, Batlle D. ACE and ACE2 activity in diabetic mice. Diabetes 55: 2132-2139, 2006
137. Xiao F, Hiremath S, Knoll G, Zimpelmann J, Srivaratharajah K, Jadhav D, Fergusson D, Kennedy CR, Burns KD. Increased urinary angiotensin-converting enzyme 2 in renal transplant patients with diabetes. PLoS One 7: e37649, 2012
138. Xu Q, Wells CC, Garman JH, Asico L, Escano CS, Maric C. Imbalance in sex hormone levels exacerbates diabetic renal disease. Hypertension 51: 1218-1224, 2008
139. Xu Y, Lin J, Wang S, Xiong J, Zhu Q. Combined estrogen replacement therapy on metabolic control in postmenopausal women with diabetes mellitus. Kaohsiung J Med Sci 30: 350-361, 2014
140. Yamaleyeva LM, Gilliam-Davis S, Almeida I, Brosnihan KB, Lindsey SH, Chappell MC. Differential regulation of circulating and renal ACE2 and ACE in hypertensive mRen2 Lewis rats with early-onset diabetes. Am J Physiol Renal Physiol 302: F1374-F1384, 2012
141. Yassin DJ, Doros G, Hammerer PG, Yassin AA. Long-term testosterone treatment in elderly men with hypogonadism and erectile dysfunction reduces obesity parameters and improves metabolic syndrome and health-related quality of life. J Sex Med 11: 1567-1576, 2014
142. Zaman MA, Oparil S, Calhoun DA. Drugs targeting the renin-angiotensin-aldosterone system. Nat Rev Drug Discov 1: 621-636, 2002
143. Zhou A, Carrell RW, Murphy MP, Wei Z, Yan Y, Stanley PL, Stein PE, Broughton Pipkin F, Read RJ. A redox switch in angiotensinogen modulates angiotensin release. Nature 468: 108-111, 2010
144. Zhou G, Cheung AK, Liu X, Huang Y. Valsartan slows the progression of diabetic nephropathy in db/db mice via a reduction in podocyte injury, and renal oxidative stress and inflammation. Clin Sci (Lond) 126: 707-720, 2014