Edgerton Dale S, Lautz Margaret, Scott Melanie, Everett Carrie A, Stettler Kathryn M, Neal Doss W, Chu Chang A, Cherrington Alan D
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
J Clin Invest. 2006 Feb;116(2):521-7. doi: 10.1172/JCI27073.
Insulin inhibits glucose production through both direct and indirect effects on the liver; however, considerable controversy exists regarding the relative importance of these effects. The first aim of this study was to determine which of these processes dominates the acute control of hepatic glucose production (HGP). Somatostatin and portal vein infusions of insulin and glucagon were used to clamp the pancreatic hormones at basal levels in the nondiabetic dog. After a basal sampling period, insulin infusion was switched from the portal vein to a peripheral vein. As a result, the arterial insulin level doubled and the hepatic sinusoidal insulin level was reduced by half. While the arterial plasma FFA level and net hepatic FFA uptake fell by 40-50%, net hepatic glucose output increased more than 2-fold and remained elevated compared with that in the control group. The second aim of this study was to determine the effect of a 4-fold rise in head insulin on HGP during peripheral hyperinsulinemia and hepatic insulin deficiency. Sensitivity of the liver was not enhanced by increased insulin delivery to the head. Thus, this study demonstrates that the direct effects of insulin dominate the acute regulation of HGP in the normal dog.
胰岛素通过对肝脏的直接和间接作用来抑制葡萄糖生成；然而，关于这些作用的相对重要性存在相当大的争议。本研究的首要目的是确定这些过程中哪一个在急性调控肝葡萄糖生成（HGP）中起主导作用。在非糖尿病犬中，使用生长抑素以及门静脉输注胰岛素和胰高血糖素来将胰腺激素钳制在基础水平。在基础采样期后，将胰岛素输注从门静脉切换至外周静脉。结果，动脉胰岛素水平翻倍，肝窦胰岛素水平减半。虽然动脉血浆游离脂肪酸（FFA）水平和肝脏FFA净摄取量下降了40 - 50%，但肝脏葡萄糖净输出增加了两倍多，且与对照组相比仍保持升高。本研究的第二个目的是确定在周围高胰岛素血症和肝脏胰岛素缺乏期间，头部胰岛素升高4倍对HGP的影响。增加向头部输送胰岛素并未增强肝脏的敏感性。因此，本研究表明，在正常犬中，胰岛素的直接作用在急性调控HGP中起主导作用。
