Skip to main content
Top
Published in: Nutrition & Metabolism 1/2012

Open Access 01-12-2012 | Research

DHEA administration and exercise training improves insulin resistance in obese rats

Authors: Koji Sato, Motoyuki Iemitsu, Katsuji Aizawa, Noboru Mesaki, Ryuichi Ajisaka, Satoshi Fujita

Published in: Nutrition & Metabolism | Issue 1/2012

Login to get access

Abstract

Background

Dehydroepiandrosterone (DHEA) is precursor of sex steroid hormone. We demonstrated that acute DHEA injection to type 1 diabetes model rats induced improvement of hyperglycemia. However, the effect of the combination of DHEA administration and exercise training on insulin resistance is still unclear. This study was undertaken to determine whether 6-weeks of DHEA administration and/or exercise training improve insulin resistance in obese male rats.

Methods

After 14 weeks of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of four groups: control, DHEA administration, exercise training, and a combination of DHEA administration and exercise training (n = 10 each group).

Results

After 6-weeks of DHEA administration and/or exercise training, rats in the combination group weighed significantly less and had lower serum insulin levels than rats in the other groups. Moreover, the rats treated with DHEA alone or DHEA and exercise had significantly lower fasting glucose levels (combination, 84 ± 6.5 mg/dL; DHEA, 102 ± 9.5 mg/dL; control, 148 ± 10.5 mg/dL). In addition, insulin sensitivity check index showed significant improvements in the combination group (combination, 0.347 ± 0.11; exercise, 0.337 ± 0.16%; DHEA, 0.331 ± 0.14; control, 0.308 ± 0.12). Muscular DHEA and 5α-dihydrotestosterone (DHT) concentrations were significantly higher in the combination group, and closely correlated with the quantitative insulin-sensitivity check index (DHEA: r = 0.71, p < 0.01; DHT: r = 0.69, p < 0.01).

Conclusion

These results showed that a combination of DHEA administration and exercise training effectively improved fasting blood glucose and insulin levels, and insulin sensitivity, which may reflect increased muscular DHEA and DHT concentrations.
Appendix
Available only for authorised users
Literature
1.
go back to reference Berdanier CD, Parente JA, McIntosh MK: Is dehydroepiandrosterone an antiobesity agent?. FASEB J. 1993, 7: 414-419. Berdanier CD, Parente JA, McIntosh MK: Is dehydroepiandrosterone an antiobesity agent?. FASEB J. 1993, 7: 414-419.
2.
go back to reference Cleary MP, Zisk JF: Anti-obesity effect of two different levels of dehydroepiandrosterone in lean and obese middle-aged female Zucker rats. Int J Obes. 1986, 10: 193-204. Cleary MP, Zisk JF: Anti-obesity effect of two different levels of dehydroepiandrosterone in lean and obese middle-aged female Zucker rats. Int J Obes. 1986, 10: 193-204.
3.
go back to reference Lea-Currie YR, Wen P, McIntosh MK: Dehydroepiandrosterone-sulfate (DHEAS) reduces adipocyte hyperplasia associated with feeding rats a high-fat diet. Int J ObesRelatMetabDisord. 1997, 21: 1058-1064. Lea-Currie YR, Wen P, McIntosh MK: Dehydroepiandrosterone-sulfate (DHEAS) reduces adipocyte hyperplasia associated with feeding rats a high-fat diet. Int J ObesRelatMetabDisord. 1997, 21: 1058-1064.
4.
go back to reference Kapoor D, Malkin CJ, Channer KS, Jones TH: Androgens, insulin resistance and vascular disease in men. Clinical Endocrinology. 2005, 63: 239-250. 10.1111/j.1365-2265.2005.02299.x.CrossRef Kapoor D, Malkin CJ, Channer KS, Jones TH: Androgens, insulin resistance and vascular disease in men. Clinical Endocrinology. 2005, 63: 239-250. 10.1111/j.1365-2265.2005.02299.x.CrossRef
5.
go back to reference Aizawa K, Iemitsu M, Otsuki T, Maeda S, Miyauchi T, Mesaki N: Sex differences in steroidogenesis in skeletal muscle following a single bout of exercise in rats. J Appl Physiol. 2008, 104: 67-74. 10.1007/s00421-008-0780-0.CrossRef Aizawa K, Iemitsu M, Otsuki T, Maeda S, Miyauchi T, Mesaki N: Sex differences in steroidogenesis in skeletal muscle following a single bout of exercise in rats. J Appl Physiol. 2008, 104: 67-74. 10.1007/s00421-008-0780-0.CrossRef
6.
go back to reference Aizawa K, Iemitsu M, Maeda S, Otsuki T, Sato K, Ushida T, Mesaki N, Akimoto T: Acute exercise activates local bioactive androgen metabolism in skeletal muscle. Steroids. 2010, 75: 219-223. 10.1016/j.steroids.2009.12.002.CrossRef Aizawa K, Iemitsu M, Maeda S, Otsuki T, Sato K, Ushida T, Mesaki N, Akimoto T: Acute exercise activates local bioactive androgen metabolism in skeletal muscle. Steroids. 2010, 75: 219-223. 10.1016/j.steroids.2009.12.002.CrossRef
7.
go back to reference Sato K, Iemitsu M, Aizawa K, Ajisaka R: DHEA improves impaired activation of Akt and PKC ζ/λ-GLUT4 pathway in skeletal muscle and improves hyperglycaemia in streptozotocin-induced diabetes rats. Acta Physiol. 2009, 197: 217-225. 10.1111/j.1748-1716.2009.02011.x.CrossRef Sato K, Iemitsu M, Aizawa K, Ajisaka R: DHEA improves impaired activation of Akt and PKC ζ/λ-GLUT4 pathway in skeletal muscle and improves hyperglycaemia in streptozotocin-induced diabetes rats. Acta Physiol. 2009, 197: 217-225. 10.1111/j.1748-1716.2009.02011.x.CrossRef
8.
go back to reference Coleman DL, Leiter EH, Schwizer RW: Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice. Diabetes. 1982, 31: 830-833. 10.2337/diabetes.31.9.830.CrossRef Coleman DL, Leiter EH, Schwizer RW: Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice. Diabetes. 1982, 31: 830-833. 10.2337/diabetes.31.9.830.CrossRef
9.
go back to reference Coleman DL, Schwizer RW, Leiter EH: Effect of genetic background on the therapeutic effects of dehydroepiandrosterone (DHEA) in diabetes-obesity mutants and in aged normal mice. Diabetes. 1984, 33: 26-32. 10.2337/diabetes.33.1.26.CrossRef Coleman DL, Schwizer RW, Leiter EH: Effect of genetic background on the therapeutic effects of dehydroepiandrosterone (DHEA) in diabetes-obesity mutants and in aged normal mice. Diabetes. 1984, 33: 26-32. 10.2337/diabetes.33.1.26.CrossRef
10.
go back to reference Cleary MP, Shephard A, Zisk J, Schwartz A: Effect of dehydroepiandrosterone on body weight and food intake in rats. NutrBehav. 1983, 1: 127-136. Cleary MP, Shephard A, Zisk J, Schwartz A: Effect of dehydroepiandrosterone on body weight and food intake in rats. NutrBehav. 1983, 1: 127-136.
11.
go back to reference Tagliaferro AR, Ronan AM, Payne J, Meeker LD, Tse S: Increased lipolysis to beta-adrenergic stimulation after dehydroepiandrosterone treatment in rats. Am J Physiol. 1995, 268: R1374-R1380. Tagliaferro AR, Ronan AM, Payne J, Meeker LD, Tse S: Increased lipolysis to beta-adrenergic stimulation after dehydroepiandrosterone treatment in rats. Am J Physiol. 1995, 268: R1374-R1380.
12.
go back to reference Mohan PF, Cleary MP: Effect of short-term DHEA administration on liver metabolism of lean and obese rats. Am J Physiol. 1988, 255: E2-E8. Mohan PF, Cleary MP: Effect of short-term DHEA administration on liver metabolism of lean and obese rats. Am J Physiol. 1988, 255: E2-E8.
13.
go back to reference Mohan PF, Ihnen JS, Levin BE, Cleary MP: Effects of dehydroepiandrosterone treatment in rats with diet-induced obesity. J Nutr. 1990, 120: 1103-1114. Mohan PF, Ihnen JS, Levin BE, Cleary MP: Effects of dehydroepiandrosterone treatment in rats with diet-induced obesity. J Nutr. 1990, 120: 1103-1114.
14.
go back to reference Han DH, Hansen PA, Chen MM: Holloszy JO.DHEA treatment reduces fat accumulation and protects against insulin resistance in male rats.J Gerontol A BiolSci. Med Sci. 1998, 53: 19-24. Han DH, Hansen PA, Chen MM: Holloszy JO.DHEA treatment reduces fat accumulation and protects against insulin resistance in male rats.J Gerontol A BiolSci. Med Sci. 1998, 53: 19-24.
15.
go back to reference Grasfeder LL, Gaillard S, Hammes SR, Ilkayeva O, Newgard CB, Hochberg RB, Dwyer MA, Chang CY, McDonnell DP: Fasting-induced hepatic production of DHEA is regulated by PGC-1[alpha], ERR[alpha], and HNF4 [alpha]. Mol Endocrinol. 2009, 23: 1171-1182. 10.1210/me.2009-0024.CrossRef Grasfeder LL, Gaillard S, Hammes SR, Ilkayeva O, Newgard CB, Hochberg RB, Dwyer MA, Chang CY, McDonnell DP: Fasting-induced hepatic production of DHEA is regulated by PGC-1[alpha], ERR[alpha], and HNF4 [alpha]. Mol Endocrinol. 2009, 23: 1171-1182. 10.1210/me.2009-0024.CrossRef
16.
go back to reference Mellon SH, Griffin LD, Compagnone NA: Biosynthesis and action of neurosteroids. Brain Res Rev. 2001, 37: 3-12. 10.1016/S0165-0173(01)00109-6.CrossRef Mellon SH, Griffin LD, Compagnone NA: Biosynthesis and action of neurosteroids. Brain Res Rev. 2001, 37: 3-12. 10.1016/S0165-0173(01)00109-6.CrossRef
17.
go back to reference Takeuchi S, Mukai N, Tateishi T, Miyakawa S: Production of sex steroid hormones from DHEA in articular chondrocyte of rats. Am J Physiol. 2007, 293: E410-E415. Takeuchi S, Mukai N, Tateishi T, Miyakawa S: Production of sex steroid hormones from DHEA in articular chondrocyte of rats. Am J Physiol. 2007, 293: E410-E415.
18.
go back to reference Sato K, Iemitsu M, Aizawa K, Ajisaka R: Testosterone and DHEA activate the glucose metabolism-related signaling pathway in skeletal muscle. Am J Physiol. 2008, 294: E961-E968. Sato K, Iemitsu M, Aizawa K, Ajisaka R: Testosterone and DHEA activate the glucose metabolism-related signaling pathway in skeletal muscle. Am J Physiol. 2008, 294: E961-E968.
19.
go back to reference Commerford SR, Ferniza JB, Bizeau ME, Thresher JS, Willis WT, Pagliassotti MJ: Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats. Am J Physiol. 2002, 283: E545-E555.CrossRef Commerford SR, Ferniza JB, Bizeau ME, Thresher JS, Willis WT, Pagliassotti MJ: Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats. Am J Physiol. 2002, 283: E545-E555.CrossRef
20.
go back to reference Levy JR, Clore JN, Stevens W: Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats. Hepatology. 2004, 39: 608-616. 10.1002/hep.20093.CrossRef Levy JR, Clore JN, Stevens W: Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats. Hepatology. 2004, 39: 608-616. 10.1002/hep.20093.CrossRef
21.
go back to reference Chen H, Sullivan G, Yue LQ, Katz A, Quon MJ: QUICKI is a useful index of insulin sensitivity in subjects with hypertension. Am J Physiol. 2003, 4: E804-E812. Chen H, Sullivan G, Yue LQ, Katz A, Quon MJ: QUICKI is a useful index of insulin sensitivity in subjects with hypertension. Am J Physiol. 2003, 4: E804-E812.
22.
go back to reference Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ: Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J clin Endocrinol Metab. 2000, 85: 2402-2410. 10.1210/jc.85.7.2402.CrossRef Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ: Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J clin Endocrinol Metab. 2000, 85: 2402-2410. 10.1210/jc.85.7.2402.CrossRef
23.
go back to reference Jessen N, Pold R, Buhl ES, Jensen LS, Schmitz O, Lund S: Effects of AICAR and exercise on insulin-stimulated glucose uptake, signalling, and GLUT4 content in rat muscles. J Appl Physiol. 2003, 94: 1373-1379.CrossRef Jessen N, Pold R, Buhl ES, Jensen LS, Schmitz O, Lund S: Effects of AICAR and exercise on insulin-stimulated glucose uptake, signalling, and GLUT4 content in rat muscles. J Appl Physiol. 2003, 94: 1373-1379.CrossRef
24.
go back to reference Hou CW, Chou SW, Ho HY, Lee WC, Lin CH, Kuo CH: Interactive effect of exercise training and growth hormone administration on glucose tolerance and muscle GLUT4 protein expression in rats. J Biomed Sci. 2003, 10: 689-696. 10.1007/BF02256320.CrossRef Hou CW, Chou SW, Ho HY, Lee WC, Lin CH, Kuo CH: Interactive effect of exercise training and growth hormone administration on glucose tolerance and muscle GLUT4 protein expression in rats. J Biomed Sci. 2003, 10: 689-696. 10.1007/BF02256320.CrossRef
25.
go back to reference Yamaguchi Y, Tanaka S, Yamakawa T, Kimura M, Ukawa K, Yamada Y, Ishihara M, Sekihara H: Reduced serum dehydroepiandrosterone levels in diabetic patients with hyperinsulinaemia. Clin Endocrinol. 1998, 49: 377-383. 10.1046/j.1365-2265.1998.00533.x.CrossRef Yamaguchi Y, Tanaka S, Yamakawa T, Kimura M, Ukawa K, Yamada Y, Ishihara M, Sekihara H: Reduced serum dehydroepiandrosterone levels in diabetic patients with hyperinsulinaemia. Clin Endocrinol. 1998, 49: 377-383. 10.1046/j.1365-2265.1998.00533.x.CrossRef
26.
go back to reference Ivy JL, Young JC, Craig BW, Kohrt WM, Holloszy JO: Ageing, exercise and food restriction: effects on skeletal glucose uptake. Mech Ageing Dev. 1991, 61: 123-133. 10.1016/0047-6374(91)90011-N.CrossRef Ivy JL, Young JC, Craig BW, Kohrt WM, Holloszy JO: Ageing, exercise and food restriction: effects on skeletal glucose uptake. Mech Ageing Dev. 1991, 61: 123-133. 10.1016/0047-6374(91)90011-N.CrossRef
27.
go back to reference Sanchez J, Heredia FP, Priego T, Portillo MP, Zamora S, Garaulet M, Palou A: Dehydroepiandrosterone prevents age-associated alterations, increasing insulin sensitivity. J Nutr Biochem. 2008, 19: 809-818. 10.1016/j.jnutbio.2007.10.005.CrossRef Sanchez J, Heredia FP, Priego T, Portillo MP, Zamora S, Garaulet M, Palou A: Dehydroepiandrosterone prevents age-associated alterations, increasing insulin sensitivity. J Nutr Biochem. 2008, 19: 809-818. 10.1016/j.jnutbio.2007.10.005.CrossRef
28.
go back to reference Jedrzejuk D, Medras M, Milewicz A, Demissie M: Dehydroepiandrosterone replacement in health men with age-related decline of DHEA-S: effects of fat distribution, insulin sensitivity and lipid metabolism. Aging male. 2003, 6: 151-156.CrossRef Jedrzejuk D, Medras M, Milewicz A, Demissie M: Dehydroepiandrosterone replacement in health men with age-related decline of DHEA-S: effects of fat distribution, insulin sensitivity and lipid metabolism. Aging male. 2003, 6: 151-156.CrossRef
29.
go back to reference Villareal DT, Hollszy JO: Effect of DHEA on abdominal fat and insulin action in elderly women and men. JAMA. 2004, 292: 2243-2248. 10.1001/jama.292.18.2243.CrossRef Villareal DT, Hollszy JO: Effect of DHEA on abdominal fat and insulin action in elderly women and men. JAMA. 2004, 292: 2243-2248. 10.1001/jama.292.18.2243.CrossRef
30.
go back to reference Nair KS, Rizza RA, O'Brien P, Dhatariya K, Short KR, Nehra A, Vittone JL, Klee GG, Basu A, Basu R, Cobelli C, Toffolo G, Dalla Man C, Tindall DJ, Melton LJ, Smith GE, Khosla S, Jensen MD: DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med. 2006, 355: 1647-1659. 10.1056/NEJMoa054629.CrossRef Nair KS, Rizza RA, O'Brien P, Dhatariya K, Short KR, Nehra A, Vittone JL, Klee GG, Basu A, Basu R, Cobelli C, Toffolo G, Dalla Man C, Tindall DJ, Melton LJ, Smith GE, Khosla S, Jensen MD: DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med. 2006, 355: 1647-1659. 10.1056/NEJMoa054629.CrossRef
Metadata
Title
DHEA administration and exercise training improves insulin resistance in obese rats
Authors
Koji Sato
Motoyuki Iemitsu
Katsuji Aizawa
Noboru Mesaki
Ryuichi Ajisaka
Satoshi Fujita
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Nutrition & Metabolism / Issue 1/2012
Electronic ISSN: 1743-7075
DOI
https://doi.org/10.1186/1743-7075-9-47

Other articles of this Issue 1/2012

Nutrition & Metabolism 1/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.