11beta-hydroxysteroid dehydrogenase type 1 activity in lean and obese males with type 2 diabetes mellitus
Valsamakis, G., Anwar, A., Tomlinson, J.W., Shackleton, C.H., McTernan, P.G., Chetty, R., Wood, P.J., Banerjee, A.K., Holder, G., Barnett, A.H., Stewart, P.M. and Kumar, S. (2004) 11beta-hydroxysteroid dehydrogenase type 1 activity in lean and obese males with type 2 diabetes mellitus. Journal of Clinical Endocrinology & Metabolism, 89, (9), 4755-4761.
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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 11beta-hydroxysteroid dehydrogenase (11beta-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/m(2) (mean +/- sd)] and 38 normal controls (age, 41.4 +/- 14 yr; BMI, 38.2 +/- 12.8 kg/m(2)).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 11beta-HSD1 activity between diabetic subjects and controls. In addition, 11beta-HSD1 activity was unaffected by BMI in diabetic subjects. However, in control subjects, increasing BMI was associated with a reduction in the urinary tetrahydrocortisol+5alpha-tetrahydrocortisol:tetrahydrocortisone ratio (P < 0.05) indicative of impaired 11beta-HSD1 activity. The degree of inhibition correlated tightly with visceral fat mass. Changes in 11beta-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 11beta-HSD1 activity in patients with diabetes may potentiate dyslipidemia, insulin resistance, and obesity. Inhibition of 11beta-HSD1 may therefore represent a therapeutic strategy in patients with type 2 diabetes mellitus and obesity.
|Keywords:||age factors, weight, glucose intolerance, obesity, role, 11-beta-hydroxysteroid dehydrogenase type 1, insulin, cortisone, cortisol, hydrocortisone, middle aged, glucocorticoids, body mass index, patients, glucose, cholesterol, aged, european continental ancestry group, enzymology, diabetes mellitus, asian continental ancestry group, adult, activity, homeostasis, weight gain, type 2, humans, diabetes mellitus, diabetes, metabolism, male, insulin resistance, thinness|
Q Science > QP Physiology
Q Science > QH Natural history > QH301 Biology
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Community Clinical Sciences
|Date Deposited:||04 Sep 2008|
|Last Modified:||27 Mar 2014 18:42|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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