Ericzon B G, Wijnen R M, Kubota K, Kootstra G, Groth C G
Department of Transplantation Surgery, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden.
Transplantation. 1992 Oct;54(4):615-20. doi: 10.1097/00007890-199210000-00009.
The effect of FK506 on glucose metabolism was studied in five cynomolgus monkeys after pancreatic transplantation and in 10 nontransplanted cynomolgus monkeys. We have clearly demonstrated that FK506 can induce hyperglycemia in these animals. In the orally treated nontransplanted animals the hyperglycemia was usually very mild (4.5-6.0 mmol/L). In one of the five transplanted animals, hyperglycemia was induced by the FK506 treatment, since histological signs of rejection were absent and since plasma glucose levels normalized on dose reduction. The glucose disappearance rates, as indicated by the K-values, decreased from a mean of 3.0 +/- 0.5%/min before FK506 treatment to 2.4 +/- 0.6%/min at one month and 1.5 +/- 0.4%/min at three months in the nontransplanted animals. In the transplant group, the K values decreased significantly from 4.2 +/- 0.6%/min in the donor animals to 1.4 +/- 0.4%/min at day 10 posttransplantation (P < 0.02). At one and three months postoperatively, the mean K-values were 1.4 +/- 0.2%/min and 1.2 +/- 0.6%/min, respectively. We conclude that FK506 is diabetogenic in the cynomolgus monkey. This side effect, however, was found to be reversible on dose reduction.
在5只胰腺移植后的食蟹猴和10只未移植的食蟹猴中研究了FK506对葡萄糖代谢的影响。我们已经清楚地证明，FK506可在这些动物中诱发高血糖。在口服给药的未移植动物中，高血糖通常非常轻微（4.5 - 6.0 mmol/L）。在5只移植动物中的1只中，FK506治疗诱发了高血糖，因为没有排斥反应的组织学迹象，并且在降低剂量后血浆葡萄糖水平恢复正常。在未移植的动物中，以K值表示的葡萄糖消失率从FK506治疗前的平均3.0±0.5%/min降至1个月时的2.4±0.6%/min和3个月时的1.5±0.4%/min。在移植组中，K值从供体动物的4.2±0.6%/min显著降至移植后第10天的1.4±0.4%/min（P < 0.02）。术后1个月和3个月时，平均K值分别为1.4±0.2%/min和1.2±0.6%/min。我们得出结论，FK506在食蟹猴中具有致糖尿病作用。然而，发现这种副作用在降低剂量后是可逆的。
