This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kimura, M. Articles by Sekihara, H. Search for Related Content PubMed PubMed Citation Articles by Kimura, M. Articles by Sekihara, H.

Dehydroepiandrosterone Decreases Serum Tumor Necrosis Factor- and Restores Insulin Sensitivity: Independent Effect from Secondary Weight Reduction in Genetically Obese Zucker Fatty Rats¹

The Third Department of Internal Medicine, The Laboratory Animal Facility, Yokohama City University School of Medicine, 3–9 Fuku-ura, Kanazawa-ku, Yokohama 236, Japan

Address all correspondence and requests for reprints to: Shun-ichi Tanaka M.D., Ph. D., The Third Department of Internal Medicine, Yokohama City University School of Medicine, 3–9 Fuku-ura, Kanazawa-ku, Yokohama 236, Japan.

Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant circulating adrenal steroids in humans. Administration of DHEA has been reported to have beneficial effects on obesity, hyperlipidemia, diabetes, and atherosclerosis in obese rodents, although its effects on insulin resistance have not been fully elucidated.

In this study, the effects of DHEA treatment on insulin sensitivity were investigated in genetically obese Zucker rats, an animal model of insulin resistance, using the euglycemic clamp technique. After 0.4% DHEA was administered for 10 days to female obese Zucker rats aged 16 weeks, body weight and plasma insulin decreased and glucose disposal rate (GDR), which was normally reduced in obese rats, rose significantly compared with age- and sex-matched control obese rats. On the other hand, although the pair-fed obese rats also showed levels of weight reduction similar to those of DHEA-treated rats, the increase in GDR of DHEA-treated rats was significantly greater than in pair-fed rats, suggesting a direct ameliorating effect of DHEA on insulin sensitivity of obese rats. Serum concentration of tumor necrosis factor (TNF)-, one of cytokines causing insulin resistance, was also reduced significantly in DHEA-treated, but not in pair-fed obese rats. In conclusion, our results suggest that DHEA treatment reduces body weight and serum TNF- independently, and that both may ameliorate insulin resistance in obese Zucker fatty rats.

This article has been cited by other articles:

				Z. Balazs, R. A.S. Schweizer, F. J. Frey, F. Rohner-Jeanrenaud, and A. Odermatt DHEA Induces 11 -HSD2 by Acting on CCAAT/Enhancer-Binding Proteins J. Am. Soc. Nephrol., January 1, 2008; 19(1): 92 - 101. [Abstract] [Full Text] [PDF]

				M. Fukui, H. Ose, I. Nakayama, H. Hosoda, M. Asano, M. Kadono, S.-i. Mogami, G. Hasegawa, T. Yoshikawa, and N. Nakamura Association Between Urinary Albumin Excretion and Serum Dehydroepiandrosterone Sulfate Concentrations in Women With Type 2 Diabetes Diabetes Care, July 1, 2007; 30(7): 1886 - 1888. [Full Text] [PDF]

				N. GALINDO-SEVILLA, N. SOTO, J. MANCILLA, A. CERBULO, E. ZAMBRANO, R. CHAVIRA, and J. HUERTO LOW SERUM LEVELS OF DEHYDROEPIANDROSTERONE AND CORTISOL IN HUMAN DIFFUSE CUTANEOUS LEISHMANIASIS BY LEISHMANIA MEXICANA Am J Trop Med Hyg, March 1, 2007; 76(3): 566 - 572. [Abstract] [Full Text] [PDF]

				H. M. Coutinho, T. Leenstra, L. P. Acosta, R. M. Olveda, S. T. McGarvey, J. F. Friedman, and J. D. Kurtis Higher Serum Concentrations of DHEAS Predict Improved Nutritional Status in Helminth-Infected Children, Adolescents, and Young Adults in Leyte, the Philippines J. Nutr., February 1, 2007; 137(2): 433 - 439. [Abstract] [Full Text] [PDF]

				M. Fukui, Y. Kitagawa, N. Nakamura, M. Kadono, G. Hasegawa, and T. Yoshikawa Association Between Urinary Albumin Excretion and Serum Dehydroepiandrosterone Sulfate Concentration in Male Patients With Type 2 Diabetes: A possible link between urinary albumin excretion and cardiovascular disease Diabetes Care, December 1, 2004; 27(12): 2893 - 2897. [Abstract] [Full Text] [PDF]

				C. M. Wheatley, S. Rattigan, S. M. Richards, E. J. Barrett, and M. G. Clark Skeletal muscle contraction stimulates capillary recruitment and glucose uptake in insulin-resistant obese Zucker rats Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E804 - E809. [Abstract] [Full Text] [PDF]

				C. J. Malkin, P. J. Pugh, R. D. Jones, D. Kapoor, K. S. Channer, and T. H. Jones The Effect of Testosterone Replacement on Endogenous Inflammatory Cytokines and Lipid Profiles in Hypogonadal Men J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3313 - 3318. [Abstract] [Full Text] [PDF]

				S. Perrini, A. Natalicchio, L. Laviola, G. Belsanti, C. Montrone, A. Cignarelli, V. Minielli, M. Grano, G. De Pergola, R. Giorgino, et al. Dehydroepiandrosterone Stimulates Glucose Uptake in Human and Murine Adipocytes by Inducing GLUT1 and GLUT4 Translocation to the Plasma Membrane Diabetes, January 1, 2004; 53(1): 41 - 52. [Abstract] [Full Text] [PDF]

				K. Kajita, T. Ishizuka, T. Mune, A. Miura, M. Ishizawa, Y. Kanoh, Y. Kawai, Y. Natsume, and K. Yasuda Dehydroepiandrosterone Down-Regulates the Expression of Peroxisome Proliferator-Activated Receptor {gamma} in Adipocytes Endocrinology, January 1, 2003; 144(1): 253 - 259. [Abstract] [Full Text] [PDF]

				P. J. Pugh, R. D. Jones, T.H. Jones, and K. S. Channer Heart failure as an inflammatory condition: potential role for androgens as immune modulators Eur J Heart Fail, December 1, 2002; 4(6): 673 - 680. [Abstract] [Full Text] [PDF]

				M. G. Wallis, C. M. Wheatley, S. Rattigan, E. J. Barrett, A. D.H. Clark, and M. G. Clark Insulin-Mediated Hemodynamic Changes Are Impaired in Muscle of Zucker Obese Rats Diabetes, December 1, 2002; 51(12): 3492 - 3498. [Abstract] [Full Text] [PDF]

				J. Pfeilschifter, R. Koditz, M. Pfohl, and H. Schatz Changes in Proinflammatory Cytokine Activity after Menopause Endocr. Rev., February 1, 2002; 23(1): 90 - 119. [Abstract] [Full Text] [PDF]

				S. J. Pan, J. Hancock, Z. Ding, D. Fogt, M. Lee, and J. L. Ivy Effects of clenbuterol on insulin resistance in conscious obese Zucker rats Am J Physiol Endocrinol Metab, April 1, 2001; 280(4): E554 - E561. [Abstract] [Full Text] [PDF]

				P.J. Pugh, K.M. English, T.H. Jones, and K.S. Channer Testosterone: a natural tonic for the failing heart? QJM, October 1, 2000; 93(10): 689 - 694. [Full Text] [PDF]

				A. Johansson, K. Carlström, B. Ahrén, K. Cederquist, E. Krylborg, H. Forsberg, and T. Olsson Abnormal Cytokine and Adrenocortical Hormone Regulation in Myotonic Dystrophy J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3169 - 3176. [Abstract] [Full Text]

				R. H. Straub, T. Gluck, M. Cutolo, J. Georgi, K. Helmke, J. Scholmerich, P. Vaith, and B. Lang The adrenal steroid status in relation to inflammatory cytokines (interleukin-6 and tumour necrosis factor) in polymyalgia rheumatica Rheumatology, June 1, 2000; 39(6): 624 - 631. [Abstract] [Full Text] [PDF]

				L. Poretsky, N. A. Cataldo, Z. Rosenwaks, and L. C. Giudice The Insulin-Related Ovarian Regulatory System in Health and Disease Endocr. Rev., August 1, 1999; 20(4): 535 - 582. [Abstract] [Full Text] [PDF]