Ricordi C, Zeng Y J, Alejandro R, Tzakis A, Venkataramanan R, Fung J, Bereiter D, Mintz D H, Starzl T E
Department of Surgery, University of Pittsburgh, Pennsylvania 15213.
Transplantation. 1991 Sep;52(3):519-22. doi: 10.1097/00007890-199109000-00026.
The purpose of this study was to evaluate the in vivo effect of FK506 on human pancreatic islets. Twenty-five nude mice were made diabetic by one intravenous injection of streptozotocin. Approximately 600 islets were administered in the renal subcapsular space 3-5 days following streptozotocin administration. One week after transplantation, the mice were divided in four groups. In group 1, the animals received 1 injection of 0.5 ml of diluent i.p. daily for one week. In groups 2, 3, and 4 the treatments were daily i.p. injection of 0.3, 1, and 3 mg/kg FK506, respectively. After treatment, the functional integrity of the transplanted human islets was tested by measuring the plasma glucose and human C-peptide response to intraperitoneal glucose injection in groups 1 and 4. IPGTT alone was assessed in groups 2 and 3. The results indicate that i.p. administration of FK506 for one week at a dose 0.3 mg/kg/day did not result in any significant alteration of glucose disappearance and C-peptide response to IPGTT. Higher doses of FK506 produced a significant delay in glucose disappearance in groups 3 and 4, and a significant inhibition of glucose-mediated C-peptide response in group 4.
本研究的目的是评估FK506对人胰岛的体内作用。通过单次静脉注射链脲佐菌素使25只裸鼠患糖尿病。在注射链脲佐菌素后3 - 5天，将约600个胰岛植入肾被膜下间隙。移植一周后，将小鼠分为四组。第1组动物每天腹腔注射0.5 ml稀释剂，共注射一周。第2、3、4组的处理分别是每天腹腔注射0.3、1和3 mg/kg FK506。处理后，通过测量第1组和第4组腹腔注射葡萄糖后的血浆葡萄糖和人C肽反应来检测移植的人胰岛的功能完整性。第2组和第3组仅评估腹腔葡萄糖耐量试验（IPGTT）。结果表明，以0.3 mg/kg/天的剂量腹腔注射FK506一周，并未导致葡萄糖清除和IPGTT的C肽反应发生任何显著改变。更高剂量的FK506使第3组和第4组的葡萄糖清除显著延迟，并使第4组的葡萄糖介导的C肽反应受到显著抑制。
