Dehydroepiandrosterone replacement in healthy men with age-related decline of DHEA-S: effects on fat distribution, insulin sensitivity and lipid metabolism

Jędrzejuk, Diana; Mędraś, M; Milewicz, A.; Demissie, Marek

doi:10.1080/713604785

Cited by 25 publications

(31 citation statements)

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“…However, conflicting results have been obtained in investigations of the effects of testosterone on insulin sensitivity in humans, depending on age, fat mass and basal testosterone levels. For example, insulin sensitivity was not changed by increasing doses of testosterone in young and healthy men (30), and testosterone had no effect on insulin action in normal young men (31) or in men with hypogonadism (32,33). In animals, administration of testosterone to castrated male rats has been shown to induce insulin resistance (34).…”

Section: Discussionmentioning

confidence: 99%

Modulation of Insulin Sensitivity and Caveolin-1 Expression by Orchidectomy in a Nonobese Type 2 Diabetes Animal Model

Lee

Cheon

et al. 2010

Mol Med

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Previously, we found that male JYD mice developed type 2 diabetes but female mice did not, and that decreased expression levels of caveolin-1 were correlated with the development of a diabetic phenotype in these mice. Therefore, we hypothesized that sex hormones affect the expression of caveolin-1 and contribute to the development of insulin resistance and hyperglycemia in JYD mice. We used glucose and insulin tolerance tests to examine insulin sensitivity in male, female and orchidectomized male JYD mice. Glucose uptake was analyzed by using 18 F-fluorodeoxyglucose positron emission tomography. We also examined insulin-signaling molecules and caveolin proteins in various tissues in these mice by Western blotting. In addition, we examined changes of caveolin-1 expression in L6 skeletal muscle cells treated with 17-β estradiol or dihydroxytestosterone. We found that glucose and insulin tolerance were impaired and hyperglycemia developed in male, but not female, JYD mice. Expression of insulin-signaling molecules such as insulin receptor, protein kinase B, and glucose transporter-4 were decreased in male JYD mice compared with female mice. Orchidectomized JYD male mice showed improved glucose and insulin tolerance with a concomitant increase in the expression of insulin-signaling molecules and caveolin-1 in adipose tissue and skeletal muscle. Moreover, 17-β-estradiol treatment increased the expression of caveolin-1 in differentiated skeletal muscle cells. We conclude that sex hormones modulate the expression of caveolin-1 and insulin-signaling molecules, subsequently affecting insulin sensitivity and the development of type 2 diabetes in JYD mice.

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Section: Discussionmentioning

confidence: 99%

Modulation of Insulin Sensitivity and Caveolin-1 Expression by Orchidectomy in a Nonobese Type 2 Diabetes Animal Model

Lee

Cheon

et al. 2010

Mol Med

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“…The known signaling mechanisms impacting glycemic control include GLUT-4−related pathways, e.g., PI3-kinase−associated Akt and PKC activation via insulin and IRS-1 [3]. GLUT-4 signaling is impaired in type 2 diabetes patient and type 2 model rats [16,22], but can be at least partially restored through exercise [1,3]. In the present study, 6 weeks of exercise improved the activation of PI3-kinase, Akt and PKCζ/λ-GLUT-4 pathways in the skeletal muscle of type 2 diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

“…The beneficial effects of exercise on type 2 diabetics have been welldocumented, including restoration of glycemic control [1][2][3]. At the molecular level, an increase in the translocation of glucose transporter 4 (GLUT-4) following the activation of phosphatidylinositol 3-kinase (PI3-kinase), and protein kinases B (Akt) and C ζ/λ (PKCζ/λ) improves glycemic control [4,5].…”

Section: Introductionmentioning

confidence: 99%

The Exercise-Induced Improvement in hyperglycemia is Mediated by DHT Produced in the Skeletal Muscle of Zucker Diabetic Fatty Rats

Sato¹

2012

J Diabetes Metab

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The ability of exercise to improve hyperglycemia by enhancing glucose metabolism in the skeletal muscle of type 2 diabetic patients is well established. We reported sex steroid hormones can be locally synthesized in skeletal muscle and decrease fasting blood glucose levels in obese rats. Here, we determined whether exercise-induced production of sex steroid hormones in skeletal muscle could directly reverse hyperglycemia in the Zucker diabetic fatty rat model using osmotic mini pump.Thirty Zucker diabetic fatty rats were randomly assigned to the following groups: control, exercise, or exercise with continuous infusion of 5α-reductase inhibitor.The results indicated 6 weeks of exercise significantly reduced serum insulin and fasting glucose levels compared to control group. Dehydroepiandrosterone, 5α-dehydrotestosterone, and 5α-reductase levels were all significantly higher in skeletal muscle of the exercise group. Moreover, exercise increased glucose transporter-4 translocation with a concomitant upregulation of phosphorylated phosphoinositide 3-kinase, protein kinase B and C-ζ/λ. Furthermore, significant correlations were observed between fasting glucose and muscular DHT levels. Interestingly, the observed exercise-induced improvements in serum insulin and fasting glucose levels were all suppressed by administration of 5α-reductase inhibitor.These results indicated the exercise-induced improvements in glucose metabolism signaling and glucose levels may be directly attributed to the increased levels of sex steroid hormones within skeletal muscles.

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“…Testosterone receptors are present on muscle (29), and some (6,13,14), but not all (15,16,19), studies have suggested that treatment with androgens can improve insulin action in rats (6) or middle-aged humans (13,14). We have previously reported that testosterone replacement in elderly men does not improve net insulin action measured with the unlabeled oral minimal model (20).…”

Section: Plasma Testosterone and Estrogen Concentrations And Body Commentioning

confidence: 99%

“…Low testosterone concentrations are associated with insulin resistance and predict the development of diabetes in elderly men (8 -12). Furthermore, androgen treatment improves insulin action in abdominally obese middle-aged men (13,14), whereas testosterone has been reported to have no effect on insulin action in normal young men (15) or in men with hypogonadism (16). Additionally, supraphysiologic doses of androgens cause insulin resistance in both humans (17,18) and dogs (19).…”

mentioning

confidence: 99%

Effect of 2 Years of Testosterone Replacement on Insulin Secretion, Insulin Action, Glucose Effectiveness, Hepatic Insulin Clearance, and Postprandial Glucose Turnover in Elderly Men

et al. 2007

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OBJECTIVE -We sought to determine whether, and if so the mechanism by which, testosterone replacement improves carbohydrate tolerance.RESEARCH DESIGN AND METHODS -Fifty-five elderly men with relative testosterone deficiency ingested a labeled mixed meal and underwent a frequently sampled labeled intravenous glucose tolerance test before and after either placebo or treatment with testosterone patch (5 mg/day) for 2 years.RESULTS -Despite restoring bioavailable testosterone to values observed in young men, the change (24 months minus baseline values) in fasting and postprandial glucose, insulin, and C-peptide concentrations and meal appearance, glucose disposal, and endogenous glucose production were virtually identical to those observed after 2 years of placebo. The change over time in insulin and C-peptide concentrations post-intravenous glucose injection also did not differ. Furthermore, the change over time in insulin action and glucose effectiveness (measured with the unlabeled and labeled "oral" and "intravenous" minimal models), as well as insulin secretion and hepatic insulin clearance (measured with the C-peptide model), did not differ in the testosterone and placebo groups.CONCLUSIONS -We conclude that 2 years of treatment with testosterone in elderly men does not improve carbohydrate tolerance or alter insulin secretion, insulin action, glucose effectiveness, hepatic insulin clearance, or the pattern of postprandial glucose metabolism. Thus, testosterone deficiency is unlikely the cause of the age-associated deterioration in glucose tolerance commonly observed in elderly men. Diabetes Care 30:1972-1978, 2007T estosterone concentrations fall and glucose tolerance deteriorates in men as they age (1-5). Currently, it is not known whether the former contributes to the latter. Data from both animal and human studies suggest this may be the case. In rats, castration decreases insulin-stimulated glucose uptake and reduces insulin gene expression in pancreatic ␤-cells (6,7). In contrast, testosterone replacement restores insulin action, increases islet insulin content, and enhances insulin secretion (6,7). Low testosterone concentrations are associated with insulin resistance and predict the development of diabetes in elderly men (8 -12). Furthermore, androgen treatment improves insulin action in abdominally obese middle-aged men (13,14), whereas testosterone has been reported to have no effect on insulin action in normal young men (15) or in men with hypogonadism (16). Additionally, supraphysiologic doses of androgens cause insulin resistance in both humans (17,18) and dogs (19).We recently reported that 24 months of dehydroepiandrosterone (DHEA) replacement in physiological doses had no beneficial effects on quality of life, body composition, or physical performance in either elderly men or women (20). We also observed that DHEA replacement did not alter net insulin action measured with the unlabeled meal minimal model (21). To our knowledge, the effects of testosterone replacement on insulin secretion, insul...

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Dehydroepiandrosterone replacement in healthy men with age-related decline of DHEA-S: effects on fat distribution, insulin sensitivity and lipid metabolism

Cited by 25 publications

References 0 publications

Modulation of Insulin Sensitivity and Caveolin-1 Expression by Orchidectomy in a Nonobese Type 2 Diabetes Animal Model

Modulation of Insulin Sensitivity and Caveolin-1 Expression by Orchidectomy in a Nonobese Type 2 Diabetes Animal Model

The Exercise-Induced Improvement in hyperglycemia is Mediated by DHT Produced in the Skeletal Muscle of Zucker Diabetic Fatty Rats

Effect of 2 Years of Testosterone Replacement on Insulin Secretion, Insulin Action, Glucose Effectiveness, Hepatic Insulin Clearance, and Postprandial Glucose Turnover in Elderly Men

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