Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Diabetes. 2012 Oct;61(10):2433-41. doi: 10.2337/db11-1816. Epub 2012 Jun 11.
We previously showed that hepatic nitric oxide regulates net hepatic glucose uptake (NHGU), an effect that can be eliminated by inhibiting hepatic soluble guanylate cyclase (sGC), suggesting that the sGC pathway is involved in the regulation of NHGU. The aim of the current study was to determine whether hepatic cyclic guanosine monophosphate (cGMP) reduces NHGU. Studies were performed on conscious dogs with transhepatic catheters. A hyperglycemic-hyperinsulinemic clamp was established in the presence of portal vein glucose infusion. 8-Br-cGMP (50 µg/kg/min) was delivered intraportally, and either the glucose load to the liver (CGMP/GLC; n = 5) or the glucose concentration entering the liver (CGMP/GCC; n = 5) was clamped at 2× basal. In the control group, saline was given intraportally (SAL; n = 10), and the hepatic glucose concentration and load were doubled. 8-Br-cGMP increased portal blood flow, necessitating the two approaches to glucose clamping in the cGMP groups. NHGU (mg/kg/min) was 5.8 ± 0.5, 2.7 ± 0.5, and 4.8 ± 0.3, whereas the fractional extraction of glucose was 11.0 ± 1, 5.5 ± 1, and 8.5 ± 1% during the last hour of the study in SAL, CGMP/GLC, and CGMP/GCC, respectively. The reduction of NHGU in response to 8-Br-cGMP was associated with increased AMP-activated protein kinase phosphorylation. These data indicate that changes in liver cGMP can regulate NHGU under postprandial conditions.
我们之前的研究表明，肝脏中的一氧化氮可以调节肝内葡萄糖净摄取（NHGU），这一效应可以通过抑制肝可溶性鸟苷酸环化酶（sGC）来消除，提示 sGC 途径参与了 NHGU 的调节。本研究旨在确定肝内环鸟苷酸（cGMP）是否会降低 NHGU。在具有经肝穿刺导管的清醒犬中进行了研究。在门静脉葡萄糖输注的情况下建立高血糖高胰岛素钳夹。门静脉内给予 8-Br-cGMP（50 µg/kg/min），并将肝脏的葡萄糖负荷（CGMP/GLC；n = 5）或进入肝脏的葡萄糖浓度（CGMP/GCC；n = 5）钳夹在基础值的 2 倍。在对照组中，门静脉内给予生理盐水（SAL；n = 10），并将肝内葡萄糖浓度和负荷加倍。8-Br-cGMP 增加门静脉血流量，需要在 cGMP 组中采用两种葡萄糖钳夹方法。NHGU（mg/kg/min）分别为 5.8 ± 0.5、2.7 ± 0.5 和 4.8 ± 0.3，而在研究的最后 1 小时，葡萄糖摄取的分数分别为 11.0 ± 1、5.5 ± 1 和 8.5 ± 1%，在 SAL、CGMP/GLC 和 CGMP/GCC 中。8-Br-cGMP 降低 NHGU 与 AMP 激活蛋白激酶磷酸化增加有关。这些数据表明，肝内 cGMP 的变化可以在餐后条件下调节 NHGU。
