Feldman J M, Plonk J W, Bivens C H, Lebovitz H E
Diabetes. 1975 Jul;24(7):664-71. doi: 10.2337/diab.24.7.664.
We assayed glucose tolerance and insulin secretion in ten patients with metastatic carcinoid tumors and the carcinoid syndrome ("active tumors") and in seven patients with metastatic carcinoid tumors without the carcinoid syndrome ("inactive tumors"). The patients with "active tumors" had elevated serum serotonin levels while the patients with "inactive tumors" had normal serum serotonin levels. Of the ten patients with "active tumors," five had diabetic and three had borderline intravenous glucose disposal rate constants (KG = 0.88 +/- 0.07, M. +/- S.E.M.). Their KG was significantly lower (p less than 0.01) than a group of age-matched normals. All of the patients with "inactive tumors" had normal KG values (KG = 1.67 +/- 0.24). Their KG did not differ from that of age-matched normal subjects. Both groups of carcinoid patients had a comparable decrease in their insulinogenic index. Two days' administration of the serotonin antagonist cyproheptadine (Cypro) to eight of the patients with "active tumors" resulted in a significant increase in the "insulinogenic index" (50%) but a nonsignificant increase in the KG (12%). Administration of p-chlorophenylalanine, a compound that blocks serotonin synthesis, resulted in an increase in both the KG (60%) and the "insulinogenic index" (55%). The insulin half-life (t1/2) of patients with "active tumors" (6.1 +/- 0.4 min.) did not differ from the t1/2 of normal subjects (6.6 +/- 0.4 min.), suggesting that the decreased plasma insulin levels following intravenous glucose were due to impaired insulin secretion rather than accelerated insulin destruction. Seven of the patients received treatment with the antitumor agent streptozotocin (Strepto). The patients received cumulative doses of from 70 to 300 mg. of Strepto per kilogram body weight with no impairment in glucose tolerance or insulin secretion. We conclude that there is high incidence of glucose intolerance (80%) and impaired insulin secretion in patients with the carcinoid syndrome and that serotonin plays a role in producing these alterations.
我们检测了10例患有转移性类癌瘤并伴有类癌综合征（“活跃肿瘤”）的患者以及7例患有转移性类癌瘤但无类癌综合征（“非活跃肿瘤”）的患者的糖耐量和胰岛素分泌情况。“活跃肿瘤”患者的血清5-羟色胺水平升高，而“非活跃肿瘤”患者的血清5-羟色胺水平正常。在10例“活跃肿瘤”患者中，5例患有糖尿病，3例的静脉葡萄糖处置速率常数处于临界值（KG = 0.88±0.07，均值±标准误）。他们的KG显著低于一组年龄匹配的正常人群（p < 0.01）。所有“非活跃肿瘤”患者的KG值均正常（KG = 1.67±0.24）。他们的KG与年龄匹配的正常受试者的KG无差异。两组类癌患者的胰岛素生成指数均有类似程度的下降。对8例“活跃肿瘤”患者给予5-羟色胺拮抗剂赛庚啶（Cypro）治疗两天后，“胰岛素生成指数”显著升高（50%），但KG升高不显著（12%）。给予对氯苯丙氨酸，一种阻断5-羟色胺合成的化合物，导致KG（60%）和“胰岛素生成指数”（55%）均升高。“活跃肿瘤”患者的胰岛素半衰期（t1/2）（6.1±0.4分钟）与正常受试者的t1/2（6.6±0.4分钟）无差异，这表明静脉注射葡萄糖后血浆胰岛素水平降低是由于胰岛素分泌受损而非胰岛素破坏加速所致。7例患者接受了抗肿瘤药物链脲佐菌素（Strepto）治疗。患者接受的链脲佐菌素累积剂量为每千克体重70至300毫克，糖耐量和胰岛素分泌均未受损。我们得出结论，类癌综合征患者中糖耐量异常（80%）和胰岛素分泌受损的发生率很高，且5-羟色胺在产生这些改变中起作用。
