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11β-Hydroxysteroid dehydrogenase Type 1 activity in lean and obese males with Type 2 diabetes mellitus
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Valsamakis, Georgios, Anwar, A., Tomlinson, J. W., Shackleton, C. H. L., McTernan, P. G. (Philip G.), Chetty, R., Wood, P. J., Banerjee, A. K., Holder, G., Barnett, A. H., Stewart, P. M. and Kumar, Sudhesh (2004) 11β-Hydroxysteroid dehydrogenase Type 1 activity in lean and obese males with Type 2 diabetes mellitus. The Journal of Clinical Endocrinology & Metabolism, Volume 89 (Number 9). pp. 4755-4761. doi:10.1210/jc.2003-032240
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Official URL: http://dx.doi.org/10.1210/jc.2003-032240
Abstract
Glucocorticoids play an important role in the pathogenesis of obesity and insulin resistance. Impaired conversion of cortisone (E) to cortisol (F) by the type 1 isoenzyme of 11β-hydroxysteroid dehydrogenase (11β-HSD) in obesity may represent a protective mechanism preventing ongoing weight gain and glucose intolerance. We have studied glucocorticoid metabolism in 33 male subjects with type 2 diabetes mellitus [age, 44.2 ± 13 yr; body mass index (BMI), 31.1 ± 7.5 kg/m2 (mean ± sd)] and 38 normal controls (age, 41.4 ± 14 yr; BMI, 38.2 ± 12.8 kg/m2).
Circulating F:E ratios were elevated in the diabetic group and correlated with serum cholesterol and homeostasis model assessment-S. There was no difference in 11β-HSD1 activity between diabetic subjects and controls. In addition, 11β-HSD1 activity was unaffected by BMI in diabetic subjects. However, in control subjects, increasing BMI was associated with a reduction in the urinary tetrahydrocortisol+5α-tetrahydrocortisol:tetrahydrocortisone ratio (P < 0.05) indicative of impaired 11β-HSD1 activity. The degree of inhibition correlated tightly with visceral fat mass. Changes in 11β-HSD1 activity could not be explained by circulating levels of adipocytokines.
Impaired E to F metabolism in obesity may help preserve insulin sensitivity and prevent diabetes mellitus. Failure to down-regulate 11β-HSD1 activity in patients with diabetes may potentiate dyslipidemia, insulin resistance, and obesity. Inhibition of 11β-HSD1 may therefore represent a therapeutic strategy in patients with type 2 diabetes mellitus and obesity
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Medicine > Warwick Medical School | ||||
| Journal or Publication Title: | The Journal of Clinical Endocrinology & Metabolism | ||||
| Publisher: | The Endocrine Society | ||||
| ISSN: | 0021-972X | ||||
| Official Date: | 2004 | ||||
| Dates: |
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| Volume: | Volume 89 | ||||
| Number: | Number 9 | ||||
| Page Range: | pp. 4755-4761 | ||||
| DOI: | 10.1210/jc.2003-032240 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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