Liver Is the Site of Splanchnic Cortisol Production in Obese Nondiabetic Humans

被引:51
作者
Basu, Rita [1 ]
Basu, Ananda [1 ]
Grudzien, Meagan [2 ]
Jung, Paul [2 ]
Jacobson, Peer [2 ]
Johnson, Michael [3 ]
Singh, Ravinder [4 ]
Sarr, Michael [5 ]
Rizza, Robert A. [1 ]
机构
[1] Mayo Clin, Coll Med, Div Endocrinol Diabet Metab & Nutr, Rochester, MN 55905 USA
[2] Abbott Labs, Global Pharmaceut Res & Dev, Abbott Pk, IL 60064 USA
[3] Mayo Clin, Coll Med, Dept Radiol, Rochester, MN USA
[4] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA
[5] Mayo Clin, Coll Med, Dept Surg, Rochester, MN USA
关键词
11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; ADIPOSE-TISSUE; HYDROXYSTEROID DEHYDROGENASE; CUSHINGS-DISEASE; IN-VIVO; MICE; METABOLISM; INSULIN; GLUCOSE; OMENTUM;
D O I
10.2337/db08-1079
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE-To determine the contribution of liver and viscera to splanchnic cortisol production in humans. RESEARCH DESIGN AND METHODS-D4 cortisol was infused intravenously; arterial, portal venous, and hepatic venous blood was sampled; and liver and visceral fat were biopsied in subjects undergoing bariatric surgery. RESULTS-Ratios of arterial and portal vein D4 cortisol/cortisolsol(total) (0.06 +/- 0.01 vs. 0.06 +/- 0.01) and D4 cortisol/D3 cortisol (1.80 +/- 0.14 vs. 1.84 +/- 0.14) did not differ, indicating that no visceral cortisol production or conversion of D4 cortisol to D3 cortisol via 11 beta-hydroxysteroid dehydrogenase type I (11 beta-HSD-1) occurred. Conversely, ratios of both D4 cortisol to cortisol(total) (0.05 +/- 0.01; P < 0.05) and D4 cortisol to D3 cortisol (1.33 +/- 0.11;P< 0.001) were lower in the hepatic vein than in the portal vein, indicating production of both cortisol and D3 cortisol by the liver. The viscera did not produce either cortisol (-8.1 +/- 2.6 mu g/min) or D3 cortisol (-0.2 +/- 0.1 mu g/min). In contrast, the liver produced both cortisol (22.7 +/- 3.90 mu g/min) and D3 cortisol (1.9 +/- 0.4 mu g/min) and accounted for all splanchnic cortisol and D3 cortisol production. Additionally, 11 beta-HSD-1 mRNA was approximately ninefold higher (P < 0.01) in liver than in visceral fat. Although 11 beta-HSD-2 gene expression was very low in visceral fat, the viscera released cortisone (P < 0.001) and D3 cortisone (P < 0.01) into the portal vein. CONCLUSIONS-The liver accounts for all splanchnic cortisol production in obese nondiabetic humans. In contrast, the viscera releases cortisone into the portal vein, thereby providing substrate for intrahepatic cortisol production. Diabetes 58:39-45, 2009
引用
收藏
页码:39 / 45
页数:7
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