Edgerton Dale S, Moore Mary C, Gregory Justin M, Kraft Guillaume, Cherrington Alan D
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Am J Physiol Endocrinol Metab. 2021 May 1;320(5):E891-E897. doi: 10.1152/ajpendo.00628.2020. Epub 2021 Apr 5.
Pancreatic insulin secretion produces an insulin gradient at the liver compared with the rest of the body (approximately 3:1). This physiological distribution is lost when insulin is injected subcutaneously, causing impaired regulation of hepatic glucose production and whole body glucose uptake, as well as arterial hyperinsulinemia. Thus, the hepatoportal insulin gradient is essential to the normal control of glucose metabolism during both fasting and feeding. Insulin can regulate hepatic glucose production and uptake through multiple mechanisms, but its direct effects on the liver are dominant under physiological conditions. Given the complications associated with iatrogenic hyperinsulinemia in patients treated with insulin, insulin designed to preferentially target the liver may have therapeutic advantages.
与身体其他部位相比，胰腺分泌的胰岛素在肝脏处形成了一个胰岛素梯度（约为3:1）。皮下注射胰岛素时，这种生理分布就会消失，导致肝脏葡萄糖生成调节受损、全身葡萄糖摄取受影响以及动脉高胰岛素血症。因此，肝门静脉胰岛素梯度对于禁食和进食期间葡萄糖代谢的正常控制至关重要。胰岛素可通过多种机制调节肝脏葡萄糖生成和摄取，但在生理条件下，其对肝脏的直接作用占主导。鉴于接受胰岛素治疗的患者存在医源性高胰岛素血症相关并发症，旨在优先作用于肝脏的胰岛素可能具有治疗优势。
