Role of endogenous androgen against insulin resistance and athero-sclerosis in men with type 2 diabetes

Current Diabetes Reviews

Volumn 3, Issue 1, 2007, Pages 25-31

  Fukui, Michiaki ^a   Kitagawa, Yoshihiro ^b   Ose, Hiroyuki ^a   Hasegawa, Goji ^a   Yoshikawa, Toshikazu ^a   Nakamura, Naoto ^a  

^a KYOTO PREFECTURAL UNIVERSITY OF MEDICINE   (Japan)

^b WEST JAPAN RAILWAY COMPANY   (Japan)

Author keywords

Atherosclerosis; Dehydroepiandrosterone; Insulin resistance; Men; Testosterone; Type 2 diabetes

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ANDROGEN; AROMATASE INHIBITOR; CELL ADHESION MOLECULE; CYTOKINE; GONADORELIN AGONIST; LIPID; METFORMIN; PLACEBO; PRASTERONE; PRASTERONE SULFATE; TESTOSTERONE;

AGING; ANDROGEN BLOOD LEVEL; ANDROGEN DEFICIENCY; ATHEROSCLEROSIS; BLOOD VESSEL REACTIVITY; CANCER HORMONE THERAPY; CARDIOVASCULAR RISK; CASTRATION; CLINICAL TRIAL; DISEASE ASSOCIATION; DISEASE SEVERITY; ERECTILE DYSFUNCTION; GLUCOSE HOMEOSTASIS; HUMAN; HYPERGLYCEMIA; HYPERLIPIDEMIA; HYPERTENSION; HYPOGONADISM; INSULIN RESISTANCE; INTRAABDOMINAL FAT; LIPID BLOOD LEVEL; LOW DRUG DOSE; MALE; METABOLIC DISORDER; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; REVIEW; SUPPLEMENTATION; TESTOSTERONE BLOOD LEVEL;

ANDROGENS; ANIMALS; ATHEROSCLEROSIS; CLINICAL TRIALS AS TOPIC; DEHYDROEPIANDROSTERONE SULFATE; DIABETES MELLITUS, TYPE 2; DIABETIC ANGIOPATHIES; HUMANS; INSULIN RESISTANCE; MALE; TESTOSTERONE;

EID: 34247103081     PISSN: 15733998     EISSN: None     Source Type: Journal    
DOI: 10.2174/157339907779802094     Document Type: Review

References (95)

1. Blouin K, Despres J-P, Couillard C, et al. Contribution of age and declining androgen levels to features of the metabolic syndrome in men. Metabolism 2005; 54: 1034-1040.
2. Howell S, Shalet S. Testosterone deficiency and replacement. Horm Res 2001; 56: 86-92.
3. Simon D, Charles MA, Nahoul K, et al. Association between plasma total testosterone and cardiovascular risk factors in healthy adult men: The Telecom Study. J Clin Endocrinol Metab 1997; 82: 682-685.
4. Haffner SM, Karhapaa P, Mykkanen L, Laakso M. Insulin resistance, body fat distribution and sex hormones in men. Diabetes 1994; 43: 12-19.
5. English KM, Steeds R, Jones TH, Channer KS. Testosterone and coronary heart disease: is there a link? Q J Med 1997; 90: 787-791.
6. Bhasin S. Effects of testosterone administration on fat distribution, insulin sensitivity, and atherosclerosis progression. Clin Infect Dis 2003; 37: S142-S149.
7. Marin P, Holmang S, Jonsson L et al. The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obes 1992; 16: 991-997.
8. Andersson B, Marin P, Lissner L, Vermeulen A, Bjontorp P. Testosterone concentrations in women and men with NIDDM. Diabetes Care 1994; 17: 405-411.
9. Barett-Connor E. Lower endogenous androgen levels and dyslipidaemia in men with NIDDM. Ann Intern Med 1992; 117: 807-811.
10. Fukui M, Koyama M, Nakagawa Y, Itoh Y, Nakamura N, Kondo M. Castration and diabetes. Diabetes Care 2000; 23: 1032-1033.
11. Jockenhovel F, Blum WF, Vogel E, et al. Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men. J Clin Endocrinol Metab 1997; 82: 2510-2513.
12. Xu X, De Pergola G, Eriksson PS, [et al. Postreceptor events involved in the up-regulation of beta-adrenergic receptor mediated lipolysis by testosterone in rat white adipocytes. Endocrinology 1993; 132: 1651-1657.
13. Stellato RK, Feldman HA, Harady O, Horton ES, McKinlay JB. Testosterone, sex hormone-binding globlin, and the development of type 2 diabetes in middle-aged men. Diabetes Care 2000; 23: 490-494.
14. Alberti KG, Zimmet P, Shaw J, for the IDF Epidemiology Task Force Consensus Group. The metabolic syndrome - a new worldwide definition. Lancet 2005; 366: 1059-1062.
15. Laaksonen DE, Niskanen L, Punnonen K, et al. Sex hormone, inflammation and the metabolic syndrome: a population-based study. Eur J Endocrinol 2003; 149: 601-608.
16. Seidell JC, Bjorntorp P, Sjostrom L, Kvist H, Sannerstedt R. Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels, but negatively with testosterone levels. Metabolism 1990; 39: 897-901.
17. Laaksonen DE, Niskanen L, Punnonen K, et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 2004; 27: 1036-1041.
18. Laaksonen DE, Niskanen L, Punnonen K, et al. The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: a prospective cohort study. J Clin Endocrinol Metab 2005; 90: 712-719.
19. Pei D, Sheu WHH, Jeng CY, Liao WK, Fuh MMT. Insulin resistance in patients with Klinnfelter's syndrome and idiopathic gonadotropin deficiency. J Formos Med Assoc 1998; 97: 534-540.
20. Faustini-Fustini M, Rochira V, Carani C. Oestrogen deficiency in men: whom are we today? Eur J Endocrinol 1999; 140: 111-129.
21. Smith EP, Boyd J, Frank GR, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 1994; 331: 1056-1061.
22. Arslanian S, Suprasongsin C. Testosterone treatment in adolescents with delayed puberty: changes in body composition, protein, fat, and glucose metabolism. J Clin Endocrinol Metab 1997; 82: 3213-3220.
23. Eakman GD, Dallas JS, Ponder SW, Keenan BS. The effects of testosterone and dihydrotestosterone on hypothalamic regulation of growth hormone secretion. J Clin Endocrinol Metab 1996; 81: 1217-1223.
24. Xu Y, Depergola G, Eriksson PS, et al. Post-receptor events involved in the up-regulation of receptor mediated lipolysis by testosterone in rat white adipocytes. Endocrinology 1993; 132: 1651-1657.
25. Marin P, Holmang S, Jonsson L, et al. The effects of testosterone treatment on body composition and metabolism in middle aged obese men. Int J Obes 1992; 16: 991-997.
26. Schroeder ET, Zheng L, Ong MD, et al. Effects of androgen therapy on adipose tissue and metabolism in older men. J Clin Endocrinol Metab 2004; 89: 4863-4872.
27. Betancourt-Albrecht M, Cunningham GR. Hypogonadism and diabetes. Int J Impot Res 2003; 15; S14-S20.
28. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004; 89: 3313-3318.
29. Whitsel EA, Boyko EJ, Matsumoto AM, Anawalt BD, Siscovick DS. Intramuscular testosterone esters and plasm lipids in hypogonadal men: a meta-analysis. Am J Med 2001; 111: 261-269.
30. Holmang A, Bjorntorp P. The effects of testosterone on insulin sensitivity in male rats. Acta Physiol Scand 1992; 146: 505-510.
31. Cohen JC, Hickman R. Insulin resistance and diminished glucose tolerance in powerlifters ingesting anabolic steroids. J Clin Endocrinol Metab 1987; 64: 960-963.
32. Boyanov MA, Boneva Z, Christov VG. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male 2003; 6:1-7.
33. Maffei L, Murata Y, Rochira V, et al. Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene: effects of testosterone, alendronate, and estradiol treatment. J Clin Endocrinol Metab 2004; 89: 61-70.
34. Inaba M, Otani Y, Nishimura K, et al. Marked hyperglycemia after androgen-deprivation therapy for prostate cancer and usefulness of pioglitazone for its treatment. Metabolism 2005; 54: 55-59.
35. Smith MR, Finkelstein JS, McGovern FJ, et al. Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab 2002; 87: 599-603.
36. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004; 89: 3313-3318.
37. Jones RD, Nettleship JE, Kapoor D, Jones HT, Channer KS. Testosterone and atherosclerosis in aging men: purported association and clinical implications. Am J Cardiovasc Drugs 2005; 5: 141-154.
38. Takeda K, Toda K, Saibara T, et al. Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency. J Endocrinol 2003; 176: 237-246.
39. Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS. Increased adipose tissue in male and female estrogen receptor- knockout-mice. Proc Natl Acad Sci USA 2000; 97: 12729-12734.
40. Nawata H, Yanase T, Goto K, Okabe T, Ashida K. Mechanism of action of anti-aging DHEA-S and the replacement of DHEA-S. Mech Ageing Dev 2002; 123: 1101-1106.
41. Ueshiba H, Shimizu Y, Hiroi N, et al. Decreased steroidogenic enzyme 17, 20-1yase and increated 17-hydroxylase activities in type 2 diabetes mellitus. Eur J Endocrinol 2002; 146: 375-380.
42. Haffner SM, Valdez RA, Stern MP, Katz MS. Obesity, body fat distribution and sex hormones in men. Int J Obes Relat Metab Disord 1993; 17: 643-649.
43. Kawano H, Yasue H, Kitagawa A, et al. Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men. J Clin Endocrinol Metab 2003; 88: 3190-3195.
44. Haffner SM, Valdez RA, Mykkanen L, Stern MP, Katz MS. Decreased testosterone and dehydroepiandrosterone sulfate concentrations; are associated with increased insulin and glucose concentrations in nondiabetic men. Metabolism 1994; 43: 599-603.
45. Nestler JE, Clore JN, Blackard WG. Dehydroepiandrosterone:the "missing link" between hyperinsulinemia and atherosclerosis? FASEB J 1992; 6: 3073-3075.
46. Nestler JE, McClanahan MA, Clore JN, Blackard WG. Insulin inhibits adrenal 17, 20-lyase activity in man. J Clin Endocrinol Metab 1992; 74: 362-367.
47. Nesder JE, Beer NA, Jakubowicz DJ, Beer RM. Effects of a reduction in circulating insulin by metformin on serum dehydro-epiandrosterone sulfate in nondiabetic men. J Clin Endocrinol Metab 1994; 78: 549-554.
48. Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men. JAMA 2004; 292: 2243-2248.
49. Kimura M, Tanaka S, Yamada Y, Kiuchi Y, Yamakawa T, Sekihara H. Dehydroepiandrosterone decreases serum tumor necrosis factor-alpha and restores insulin sensitivity: independent effect from secondary weight reduction in genetically obese Zucker fatty rats. Endocrinology 1998; 139: 3249-3253.
50. Usiskin KS, Butterworth S, Clore JN, et al. Lack of effect of dehydroepiandrosterone in obese men. Int J Obes 1990; 14: 457-463.
51. Nestler JE, Barlascini CO, Clore JN, Blackard WG. Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J Clin Endocrinol Metab 1988; 66: 57-61.
52. Arlt W, Haas J, Callies F, et al. Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens. J Clin Endocrinol Metab 1999; 84: 2170-2176.
53. Yen TT, Allan JA, Pearson DV, Acton JM, Greenberg MM. Prevention of obesity in Avy/a mice by dehydroepiandrosterone. Lipids 1977; 12: 409-413.
54. Coleman DL, Schwizer RW, Leithr EH. Effect of genetic background on the therapeutic effects of dehydroepiandrosterone (DHEA) in diabetes-obesity mutants and aged normal mice. Diabetes 1984: 33; 26-32.
55. Gordon GB, Bush DE, Weisman HF. Reduction of atherosclerosis by administration of dehydroepiandrosterone. J Clin Invest 1988; 82: 712-720.
56. Coleman DL, Leiter EH, Schwizer RW. Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice. Diabetes 1982; 31: 830-833.
57. Karbowska J, Kochan Z. Effect of DHEA on endocrine functions of adipose tissue, the involvement of PPAR. Biochem Pharmacol 2005; 70: 249-257.
58. Fukui M, Kitagawa Y, Nakamura N, et al. Association between serum testosterone concentration and carotid atherosclerosis in men with type 2 diabetes. Diabetes Care 2003; 26: 1869-1873.
59. English KM, Steeds R, Jones TH, Channer KS. Testosterone and coronary heart disease: is there a link? Q J Med 1997; 90: 787-791.
60. Phillips GB, Pinkernell BH, Jing TY. The association of hypotestosteronaemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 1994; 14: 701-706.
61. Jeppeson LL, Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS, Winther K. Decreased testosterone in men with acute ischaemic stroke. Arterioscler Thromb Vasc Biol 1996; 16: 749-754.
62. Barrett-Connor E, Khaw KT. Endogenous sex hormones and cardiovascular disease in men. A prospective population based study. Circulation 1988; 78: 539-545.
63. Howell S, Shalet S. Testosterone deficiency and replacement. Horm Res 2001; 56: S86-S92.
64. Webb CM, McNeill JG, Hayward CS, de Zeigler D, Collins P. Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation 1999; 100: 1690-1696.
65. Webb CM, Adamson DL, de Zeigler D, Collins P. Effects of testosterone on myocardial ischemia in men with coronary artery disease. Am J Cardiol 1999; 83: 437-439.
66. Rosario GMC, Leonardo F, Pagnotta P, et al. Acute anti-ischaemic effect of testosterone in men with coronary artery disease. Circulation 1999; 99: 1666-1670.
67. Kang SM, Jang Y, Kim JY, et al. Effect of oral administration of testosterone on brachial arterial vasoreactivity in men with coronary artery disease. Am J Cardiol 2002; 89: 862-864.
68. Mukherjee TK, Dinh H, Chaudhuri G, Nathan L. Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: implications in atherosclerosis. Proc Natl Acad Sci USA 2002; 99: 4055-4060.
69. Sudhir K, Komesaroff P. Cardiovascular actions of estrogens in men. J Clin Endocrinol Metab 1999; 84: 3411-3415.
70. Sudhir K, Chou TM, Messina LM, et al. Endothelial dysfunction in a man with disruptive mutation in oestrogen-receptor gene. Lancet 1997; 349: 1146-1147.
71. l Aro J. Cardiovascular and all-cause mortality in prostatic cancer patients treated with estrogens or orchiectomy as compared to the standard population. Prostate 1991; 18: 131-137.
72. Blum A, Cannon III RO. Effiects of oestrogens and selective oestrogen receptor modulators on serum lipoproteins and vascular function. Curr Opin Lipidol 1998; 9: 575-586.
73. Smith JC, Benett S, Evans M et al. The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. J Clin Endocrinol Metab 2001; 86: 4261-4267.
74. Alexandersen P, Haarbo J, Byrjalsen I, Lawaetz H, Christiansen C. Natural androgens inhibit male atherosclerosis. A study of castrated, cholesterol fed rabbits. Circ Res 1999; 84: 813-819.
75. Nathan L, Shi WB, Dinh H, et al. Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase. Proc Nad Acad Sci USA 2001; 98: 3589-3593.
76. Rubanyi GM, Freay AD, Kauser K, et al. Vascular estrogen reeptors and endothelium-derived nitric oxide production in the mouse aorta. Gender difference and effect of estrogen receptor gene disruption. J Clin Invest 1997; 99: 2429-2437.
77. Deenadayalu VP, White RE, Stallone JN, et al. Testosterone relaxes coronary arteries by opening the large-conductance, calcium-activated potassium channel. Am J Physiol 2001; 281: H1720-H1727.
78. English KM, Jones RD, Jones TH, et al. Testosterone acts as a coronary vasodilator by a calcium channel antagonist action. J Endocrinol Invest 2002; 25: 455-458.
79. Fukui M, Kitagawa Y, Nakamura N, et al. Serum dehydroepiandrosterone sulfate concentration and carotid atherosclerosis in men with type 2 diabetes. Atherosclerosis 2005; 181: 339-344.
80. Hak AE, Witteman JC, deJong FH, Geerlings MI, Hofman A, Pols HA. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J Clin Endocrinol. Metab 2002; 87: 3632-3639.
81. Herrington DM, Gordon GB, Achuff SC, et al. Plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate in patients undergoing diagnostic coronary angiography. J Am Coll Cardiol 1990; 16: 862-870.
82. Eich DM, Nestler JE, Johnson DE, et al. Inhibition of accelerated coronary atherosclerosis with dehydroepiandrosterone in the heterotopic rabbit model of cardiac transplantation. Circulation 1993; 87: 261-269.
83. Gordon GB, Bush DE, Weisman HF. Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury. J Clin Invest 1988; 82: 712-720.
84. Haffner SM, Moss SE, Klein BE, Klein R. Sex hormones and DHEA-SO4 in relation to ischemic heart disease mortality in diabetic subjects. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Diabetes Care 1996; 19: 1045-1050.
85. Kiechl S, Willeit J, Bonora E, Schwarz S, Xu Q. No association between dehydroepiandrosterone sulfate and development of atherosclerosis in a prospective population study (Bruneck Study). Arterioscler Thromb Vasc Biol 2000; 20: 1094-1100.
86. Fukui M, Kitagawa Y, Nakamura N, Kadono M, Hasegawa G, Yoshikawa T. Association between alcohol consumption and serum dehydroepiandrosterone sulfate concentration in men with type 2 diabetes: a link to decreased cardiovascular risk. Diabetic Med 2005; 22: 1446-1450.
87. Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus: a systematic overview of the literature. Arch Intern Med 1997; 157: 1413-1418.
88. Fukui M, Kitagawa Y, Nakamura N, Kadono M, Hasegawa G, Yoshikawa T. Association between urinary albumin excretion and serum dehydroepiandrosterone sulfate concentration in male patients with type 2 diabetes. Diabetes Care 2004; 27: 2893-2897.
89. Furutama D, Fukui R, Amakawa M, Ohsawa N. Inhibition of migration and proliferation of vascular smooth muscle cells by dehydroepiandrosterone sulfate. Biochim Biophys Acta 1998; 1406: 107-114.
90. Okamoto K. Relationship between dehydroepiandrosterone sulfate and serum lipid levels in Japanese men. J Epidemiol 1996; 6: 63-67.
91. Jesse RL, Loesser K, Eich DM, Qian YZ, Hess ML, Nestler JE. Dehydroepiandrosterone inhibits human platelet aggregation in vitro and in vivo. Ann N Y Acad Sci 1995; 774: 281-290.
92. Barbagallo M, Shan J, Pang PK, Resnick L.M. Effects of dehydroepiandrosterone sulfate on cellular calcium responsiveness and vascular contractility. Hypertension 1995; 26: 1065-1069.
93. Straub RH, Konecna L, Hrach S, et al. Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J Clin Endocrinol Metab 1988; 83: 2012-2017.
94. Williams MR, Ling S, Dawood T, et al. Dehydroepiandrosterone inhibits human vascular smooth muscle cell proliferation independent of ARs and ERs. J Clin Endocrinol Metab 2002; 87: 176-181.
95. Niskanen L, Laaksonen DE, Punnonen K, Mustajoki P, Kaukua J, Rissanen A. Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes Obes Metab 2004; 6: 208-215.