The contribution of visceral adipose tissue to splanchnic cortisol production in healthy humans
The contribution of visceral adipose tissue to splanchnic cortisol production in healthy humans
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DOI：
10.2337/diabetes.54.5.1364
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发表时间：
2005-05-01
期刊：
影响因子：
7.7
通讯作者：
Walker, BR
中科院分区：
文献类型：
--
作者：
Andrew, R;Westerbacka, J;Walker, BR
皮质醇通过11 β-羟基类固醇脱氢酶1型（11 HSD 1）从可的松再生，增强脂肪组织和肝脏中的糖皮质激素作用。11 HSD 1抑制剂正在开发用于2型糖尿病，可能对肥胖症最有效，其中脂肪11 HSDI增加。然而，皮质醇在人类不同组织中的再生幅度是未知的，阻碍了对11 HSD 1的病理生理和治疗重要性的理解。在8名健康男性中，我们输注了9，11，12，12-H-2（4）-皮质醇，并测量了肝静脉中的示踪剂富集，作为总内脏皮质醇生成的指标。然后给予口服可的松（25 mg）以测量首过肝脏皮质醇生成。在稳定状态下，当动脉化血浆可的松浓度为92 +/- 7 nmol/l时，内脏皮质醇产生为45 +/- 11 nmol/min。口服可的松后肝皮质醇生成的外推表明，在稳态下，肝脏贡献15.2 nmol/min，肝外内脏组织贡献29.8 nmol/min的总内脏皮质醇生成。我们的结论是，组织引流到门静脉，包括内脏脂肪组织，大大有助于皮质醇的再生。因此，除了游离脂肪酸和脂肪因子外，门静脉还向肝脏输送皮质醇，抑制内脏脂肪组织中的11 HSD 1可能确实对改善肥胖症的胰岛素抵抗有价值。
Cortisol is regenerated from cortisone by 11 beta-hydroxy-steroid dehydrogenase type 1 (11HSD1), amplifying glucocorticoid action in adipose tissue and liver. 11HSD1 inhibitors are being developed for type 2 diabetes and may be most effective in obesity, where adipose 11HSDI is increased. However, the magnitude of regeneration of cortisol in different tissues in humans is unknown, hindering understanding of the pathophysiological and therapeutic importance of 11HSD1. In eight healthy men, we infused 9,11,12,12-H-2(4)-cortisol and measured tracer enrichment in the hepatic vein as an indicator of total splanchnic cortisol generation. Oral cortisone (25 mg) was then given to measure first-pass hepatic cortisol generation. In steady state, splanchnic cortisol production was 45 +/- 11 nmol/min when arterialized plasma cortisone concentration was 92 +/- 7 nmol/l. Extrapolation from hepatic cortisol generation after oral cortisone suggested that, at steady state, the liver contributes 15.2 nmol/min and extrahepatic splanchnic tissue contributes 29.8 nmol/min to the total splanchnic cortisol production. We conclude that tissues draining into the portal vein, including visceral adipose tissue, contribute substantially to the regeneration of cortisol. Thus, in addition to free fatty acids and adipokines, the portal vein delivers cortisol to the liver, and inhibition of 11HSD1 in visceral adipose tissue may indeed be valuable in ameliorating insulin resistance in obesity.