Basu Rita, Edgerton Dale S, Singh Ravinder J, Cherrington Alan, Rizza Robert A
Mayo Clinic, 200 1st St. SW, Rm 5-194 Joseph, Rochester, MN 55905, USA.
Diabetes. 2006 Nov;55(11):3013-9. doi: 10.2337/db06-0601.
Eight dogs underwent combined hepatic/portal vein catheterization and infusion of D4-cortisol in order to determine the relative contributions of the viscera and liver to splanchnic cortisol production. D4-cortisol concentrations progressively decreased from 2.6 +/- 0.1 to 2.4 +/- 0.1 to 1.7 +/- 0.1 microg/dl (P < 0.001 by ANOVA) from hepatic artery to portal vein to hepatic vein, respectively, indicating 8 +/- 3 and 28 +/- 3% extraction across the viscera and liver, respectively. On the other hand, hepatic artery, portal vein, and hepatic vein cortisol concentrations did not differ (0.31 +/- 0.12 vs. 0.28 +/- 0.11 vs. 0.27 +/- 0.10 microg/dl, respectively), indicating zero net cortisol balance. This meant that 1.0 +/- 0.1 microg/min of cortisol was produced within the splanchnic bed, all of which occurred within the liver (1.2 +/- 0.1 microg/min). On the other hand, visceral cortisol production did not differ from zero (-0.2 +/- 0.2 microg/min; P < 0.001 vs. liver). Flux through the 11beta hydroxysteroid dehydrogenase (HSD) type 1 pathway can be measured by determining the rate of conversion of D4-cortisol to D3-cortisol. D3-cortisol concentrations were lower in the portal vein than hepatic artery (0.45 +/- 0.03 vs. 0.48 +/- 0.02, respectively; P < 0.01) but did not differ in the portal vein and hepatic vein, indicating net uptake across the viscera but zero balance across the liver. D3-cortisol production with the viscera and liver averaged 0.2 +/- 0.1 microg/min (P = NS vs. zero production) and 0.6 +/- 0.1 microg/min (P < 0.001 vs. zero production; P < 0.001 vs. viscera production), respectively. We conclude that most, if not all, of splanchnic cortisol production occurs within the liver. Taken together, these data suggest that the high local cortisol concentrations generated via the 11beta HSD type 1 pathway within the liver likely contribute to the regulation of hepatic glucose, fat, and protein metabolism.
八只狗接受了肝/门静脉联合插管并输注D4-皮质醇，以确定内脏和肝脏对内脏皮质醇产生的相对贡献。从肝动脉到门静脉再到肝静脉，D4-皮质醇浓度分别从2.6±0.1微克/分升降至2.4±0.1微克/分升再降至1.7±0.1微克/分升（方差分析，P<0.001），分别表明内脏和肝脏的提取率为8±3%和28±3%。另一方面，肝动脉、门静脉和肝静脉的皮质醇浓度没有差异（分别为0.31±0.12微克/分升、0.28±0.11微克/分升和0.27±0.10微克/分升），表明皮质醇净平衡为零。这意味着在内脏床内产生了1.0±0.1微克/分钟的皮质醇，所有这些都发生在肝脏内（1.2±0.1微克/分钟）。另一方面，内脏皮质醇的产生与零没有差异（-0.2±0.2微克/分钟；与肝脏相比，P<0.001）。通过测定D4-皮质醇向D3-皮质醇的转化速率，可以测量通过11β-羟类固醇脱氢酶（HSD）1型途径的通量。门静脉中的D3-皮质醇浓度低于肝动脉（分别为0.45±0.03和0.48±0.02；P<0.01），但门静脉和肝静脉中的浓度没有差异，表明在内脏中有净摄取，但在肝脏中平衡为零。内脏和肝脏的D3-皮质醇产生平均分别为0.2±0.1微克/分钟（与零产生相比，P=无显著性差异）和0.6±0.1微克/分钟（与零产生相比，P<0.001；与内脏产生相比，P<0.001）。我们得出结论，内脏皮质醇的产生大部分（如果不是全部）发生在肝脏内。综上所述，这些数据表明，肝脏内通过11β-HSD 1型途径产生的高局部皮质醇浓度可能有助于调节肝脏的葡萄糖、脂肪和蛋白质代谢。
