Flatt P R, Tan K S, Bailey C J, Powell C J, Swanston-Flatt S K, Marks V
Br J Cancer. 1986 Oct;54(4):685-92. doi: 10.1038/bjc.1986.227.
Twenty-one days after s.c. subscapular transplantation of a radiation-induced insulinoma, male NEDH rats exhibited hyperinsulinaemia and hypoglycaemia. These features were associated with islet atrophy, degenerative changes in pancreatic A and B cells, and decreases in the pancreatic contents of insulin, glucagon and somatostatin. The immunoreactive glucagon and somatostatin contents of extrapancreatic tissues of insulinoma-bearing rats were unchanged. Surgical resection of the tumour resulted in an immediate fall of plasma insulin, attaining concentrations similar to those of anaesthetised control rats by 10 min. The estimated half-life of insulin was 3.5 min. Hypoglycaemia persisted until 60 min after resection, followed by hyperglycaemia of 1-2 days duration. Glucose tolerance was impaired 1 day after tumour resection despite the coexistence of raised insulin concentrations. Evidence for abnormal pancreatic B cell function was gained by injection of arginine which failed to evoke a plasma insulin response in the resected rats. Two days after resection, plasma glucose and insulin concentrations were similar to those of control rats. Plasma glucose and insulin responses to glucose and arginine were suggestive of tumour recurrence by 12 days. A single large encapsulated tumour was eventually observed in each rat, with resection giving a 17-56 day prolongation of life.
在皮下肩胛下移植辐射诱导的胰岛素瘤21天后,雄性NEDH大鼠出现高胰岛素血症和低血糖症。这些特征与胰岛萎缩、胰腺A细胞和B细胞的退行性变化以及胰岛素、胰高血糖素和生长抑素的胰腺含量降低有关。携带胰岛素瘤大鼠的胰腺外组织中免疫反应性胰高血糖素和生长抑素含量未发生变化。手术切除肿瘤导致血浆胰岛素立即下降,10分钟后达到与麻醉对照大鼠相似的浓度。胰岛素的估计半衰期为3.5分钟。低血糖持续到切除后60分钟,随后出现持续1 - 2天的高血糖症。尽管胰岛素浓度升高,但肿瘤切除后1天葡萄糖耐量仍受损。通过注射精氨酸未能在切除大鼠中引起血浆胰岛素反应,从而获得了胰腺B细胞功能异常的证据。切除后2天,血浆葡萄糖和胰岛素浓度与对照大鼠相似。到12天时,血浆葡萄糖和胰岛素对葡萄糖和精氨酸的反应提示肿瘤复发。最终在每只大鼠中观察到一个单一的大的包膜肿瘤,切除肿瘤使寿命延长了17 - 56天。