Jang Christina, Obeyesekere Varuni R, Dilley Rodney J, Krozowski Zygmunt, Inder Warrick J, Alford Frank P
Department of Endocrinology and Diabetes, St. Vincent's Hospital, Melbourne, 41 Victoria Parade, Fitzroy 3065, Australia.
J Clin Endocrinol Metab. 2007 Aug;92(8):3314-20. doi: 10.1210/jc.2006-2729. Epub 2007 May 22.
There is little information regarding the regulation of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes in skeletal muscle in the setting of type 2 diabetes.
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.
Participants underwent muscle biopsy of vastus lateralis at baseline and after dexamethasone.
The study took place at a university teaching hospital.
Twelve subjects with type 2 diabetes and 12 age- and sex-matched controls participated.
Subjects were given oral dexamethasone, 4 mg/d for 4 d.
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.
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).
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.
在2型糖尿病背景下，关于骨骼肌中11β-羟基类固醇脱氢酶（11β-HSD）的调控信息甚少。
我们的目的是研究与对照组相比，糖尿病患者骨骼肌中11β-HSD1和11β-HSD2在基线时以及对地塞米松反应时是否存在mRNA表达差异和酶活性差异。
参与者在基线时和使用地塞米松后接受股外侧肌肌肉活检。
该研究在一所大学教学医院进行。
12名2型糖尿病患者和12名年龄及性别匹配的对照者参与。
受试者口服地塞米松，4mg/d，共4天。
我们通过定量逆转录聚合酶链反应（RT-PCR）评估11β-HSD1、11β-HSD2和H6PDH的mRNA水平，并分别通过[³H]可的松和[³H]皮质醇的转化率评估酶活性。
在基线时，糖尿病患者和对照者中11β-HSD1、11β-HSD2和H6PDH的mRNA水平相似。糖尿病患者中11β-HSD1活性降低（[³H]可的松转化为[³H]皮质醇的转化率为11.4±2.5%，而对照组为18.5±2.2%；P = 0.041），糖尿病患者中11β-HSD2酶活性较高（[³H]可的松转化为[³H]皮质醇的转化率为17.2±2.6%，而对照组为9.2±1.3%；P = 0.012）。使用地塞米松后，两组中11β-HSD1的mRNA均增加（P < 0.001），而11β-HSD2的mRNA减少（P = 0.002）。糖尿病患者中11β-HSD1活性增加（P = 0.021），而对照组未增加，而两组中11β-HSD2活性均未改变。在基线时，11β-HSD1和11β-HSD2酶活性之间存在显著负相关（r = -0.463；P = 0.026）。
糖尿病时骨骼肌中11β-HSD1和11β-HSD2的活性发生改变，这可能共同减少细胞内皮质醇的生成，潜在地提供代谢保护。
