Altered activity of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in skeletal muscle confers metabolic protection in subjects with type 2 diabetes.
J Clin Endocrinol Metab
; 92(8): 3314-20, 2007 Aug.
Article
em En
| MEDLINE
| ID: mdl-17519316
ABSTRACT
CONTEXT There is little information regarding the regulation of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes in skeletal muscle in the setting of type 2 diabetes. OBJECTIVE:
Our objective was to investigate whether there is differential mRNA expression and enzyme activity of 11beta-HSD1 and 11beta-HSD2 in the skeletal muscle of diabetic subjects compared with controls at baseline and in response to dexamethasone.DESIGN:
Participants underwent muscle biopsy of vastus lateralis at baseline and after dexamethasone.SETTING:
The study took place at a university teaching hospital.PARTICIPANTS:
Twelve subjects with type 2 diabetes and 12 age- and sex-matched controls participated. INTERVENTION Subjects were given oral dexamethasone, 4 mg/d for 4 d. MAIN OUTCOMEMEASURES:
We assessed 11beta-HSD1, 11beta-HSD2, and H6PDH mRNA levels by quantitative RT-PCR and enzyme activity by percent conversion of [(3)H]cortisone and [(3)H]cortisol, respectively.RESULTS:
At baseline, mRNA levels were similar in diabetic and control subjects for 11beta-HSD1, 11beta-HSD2, and H6PDH. 11beta-HSD1 activity was reduced in diabetic subjects (percent conversion of [(3)H]cortisone to [(3)H]cortisol was 11.4 +/- 2.5% vs. 18.5 +/- 2.2%; P = 0.041), and 11beta-HSD2 enzyme activity was higher in diabetic subjects (percent conversion of [(3)H]cortisone to [(3)H]cortisol was 17.2 +/- 2.6% vs. 9.2 +/- 1.3%; P = 0.012). After dexamethasone, 11beta-HSD1 mRNA increased in both groups (P < 0.001), whereas 11beta-HSD2 mRNA decreased (P = 0.002). 11beta-HSD1 activity increased in diabetic subjects (P = 0.021) but not in controls, whereas 11beta-HSD2 activity did not change in either group. At baseline, there was a significant negative correlation between 11beta-HSD1 and 11beta-HSD2 enzyme activity (r = -0.463; P = 0.026).CONCLUSIONS:
The activities of skeletal muscle 11beta-HSD1 and 11beta-HSD2 are altered in diabetes, which together may reduce intracellular cortisol generation, potentially conferring metabolic protection.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Músculo Esquelético
/
11-beta-Hidroxiesteroide Desidrogenase Tipo 1
/
11-beta-Hidroxiesteroide Desidrogenase Tipo 2
/
Diabetes Mellitus Tipo 2
Limite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Austrália