Strasser S, Alejandro R, Shapiro E T, Ricordi C, Todo S, Mintz D H
Diabetes Research Institute, University of Miami School of Medicine, FL 33101.
Metabolism. 1992 Jan;41(1):64-7. doi: 10.1016/0026-0495(92)90192-d.
In this report, we describe the effect of FK506 on glucose-mediated insulin release in normal dogs. Dogs were placed into one of two groups, group 1 dogs received FK506 (1 mg/kg/d orally) for 2 weeks, and group 2 dogs received FK506 at the same dose, but for 4 weeks. Following the treatment period, both groups of dogs were allowed a recovery period during which time no FK506 was administered. Intravenous glucose tolerance tests (IVGTT) were performed (0.5 mg/kg IV) before FK506 treatment, after 2 or 4 weeks of treatment, and following the recovery periods. Complete blood cell counts (CBC) and serum chemistries were also obtained at these times. Following FK506 treatment for either 2 or 4 weeks, the dogs experienced a delay in glucose disappearance in response to IV glucose injection. Insulin secretion during IVGTT was unchanged in dogs treated for only 2 weeks, but was significantly decreased in dogs treated for 4 weeks. Following the recovery period, glucose disappearance during IVGTT returned to normal in dogs that were treated for 2 weeks, and was more rapid than normal in dogs that had been treated for 4 weeks. Insulin secretion after the recovery period remained unchanged in group 1 dogs, but continued to be significantly reduced in group 2 dogs that had received FK506 for 4 weeks. No significant change was detected in the CBCs or serum chemistries.
在本报告中，我们描述了FK506对正常犬葡萄糖介导的胰岛素释放的影响。犬被分为两组，第1组犬口服FK506（1毫克/千克/天），持续2周，第2组犬接受相同剂量的FK506，但持续4周。治疗期结束后，两组犬均有一段恢复期，在此期间不给予FK506。在FK506治疗前、治疗2周或4周后以及恢复期后进行静脉葡萄糖耐量试验（IVGTT，静脉注射0.5毫克/千克）。在这些时间点还进行了全血细胞计数（CBC）和血清化学检测。在接受FK506治疗2周或4周后，犬对静脉注射葡萄糖的葡萄糖消失出现延迟。仅接受2周治疗的犬在IVGTT期间胰岛素分泌未改变，但接受4周治疗的犬胰岛素分泌显著减少。恢复期后，接受2周治疗的犬在IVGTT期间葡萄糖消失恢复正常，而接受4周治疗的犬葡萄糖消失比正常情况更快。第1组犬恢复期后的胰岛素分泌保持不变，但接受FK506治疗4周的第2组犬胰岛素分泌仍显著降低。CBC或血清化学检测未发现显著变化。
