Meier Juris J, Hong-McAtee Irene, Galasso Ryan, Veldhuis Johannes D, Moran Antoinette, Hering Bernhard J, Butler Peter C
Larry Hillblom Islet Research Center, University of California Los Angeles David Geffen School of Medicine, 24-130 Warren Hall, 900 Veteran Ave., 90095-7073, USA.
Diabetes. 2006 Aug;55(8):2324-32. doi: 10.2337/db06-0069.
Intrahepatic islet transplantation is an experimental therapy for type 1 diabetes. In the present studies, we sought to address the following questions: 1) In humans, do intrahepatic transplanted islets reestablish coordinated puslatile insulin secretion? and 2) To what extent is insulin secreted by intrahepatic transplanted islets delivered to the hepatic sinusoids (therefore effectively restoring a portal mode of insulin delivery) versus delivered to the hepatic central vein (therefore effectively providing a systemic form of insulin delivery)? To address the first question, we examined insulin concentration profiles in the overnight fasting state and during a hyperglycemic clamp ( approximately 150 mg/dl) in 10 recipients of islet transplants and 10 control subjects. To address the second question, we measured first-pass hepatic insulin clearance in two recipients of islet autografts after pancreatectomy for pancreatitis versus five control subjects by direct catheterization of the hepatic vein. We report that coordinate pulsatile insulin secretion is reestablished in islet transplant recipients and that glucose-mediated stimulation of insulin secretion is accomplished by amplification of insulin pulse mass. Direct hepatic catheterization studies revealed that intrahepatic islets in humans do deliver insulin directly to the hepatic sinusoid because approximately 80% of the insulin is extracted during first pass. In conclusion, intrahepatic islet transplantation effectively restores the liver to pulsatile insulin delivery.
肝内胰岛移植是一种针对1型糖尿病的实验性治疗方法。在本研究中，我们试图解决以下问题：1）在人类中，肝内移植的胰岛能否重新建立协调性的脉冲式胰岛素分泌？以及2）肝内移植的胰岛分泌的胰岛素在多大程度上是输送到肝血窦（从而有效地恢复门静脉胰岛素输送模式），而不是输送到肝中央静脉（从而有效地提供全身性胰岛素输送形式）？为了解决第一个问题，我们在10名胰岛移植受者和10名对照受试者中，检测了过夜禁食状态和高血糖钳夹（约150mg/dl）期间的胰岛素浓度曲线。为了解决第二个问题，我们通过直接经肝静脉插管，测量了两名因胰腺炎行胰腺切除术后胰岛自体移植受者与五名对照受试者的肝首过胰岛素清除率。我们报告，胰岛移植受者中重新建立了协调性的脉冲式胰岛素分泌，并且葡萄糖介导的胰岛素分泌刺激是通过胰岛素脉冲量的放大来实现的。直接肝插管研究显示，人类肝内胰岛确实将胰岛素直接输送到肝血窦，因为约80%的胰岛素在首过期间被摄取。总之，肝内胰岛移植有效地恢复了肝脏的脉冲式胰岛素输送。
