Ueki M, Yasunami Y, Motoyama K, Funakoshi A, Ikeda S, Tanaka M
Department of Surgery I, Faculty of Medicine Kyushu University, Fukuoka, Japan.
Transplantation. 1995 Aug 27;60(4):313-7. doi: 10.1097/00007890-199508270-00001.
The purpose of the present study was to determine whether or not hyperglycemia in streptozotocin (STZ)-induced diabetic rats after the intraportal transplantation of an insufficient number of isogenic islets can be ameliorated by nicotinamide treatment. WKA/Qdj (RT 1u) rats were used both as donors and recipients. Islets were isolated by the collagenase technique. A total of 350 islets was transplanted into the liver via the portal vein of the STZ-induced diabetic rats. Either nicotinamide (NA, 0.5 g/kg) or a vehicle (saline) was administered ip once a day for 60 days after transplantation. All the diabetic rats without islet transplantation remained hyperglycemic irrespective of the NA treatment. All the recipients (n = 12) bearing the islet grafts and treated with saline remained hyperglycemic (> 400 mg/dl) at 60 days after transplantation. In marked contrast, all the recipients (n = 18) with islet grafts and treated with NA became normoglycemic (< 200 mg/dl) at 16.2 +/- 7.1 days (mean +/- SD) after transplantation. Morphologically, islets were easily found in the liver of the recipients. Aldehyde-fuchsin stain revealed that the beta cells in the islet grafts of the NA treated recipients were well granulated, whereas those treated with saline were degranulated. The insulin content of the liver bearing the grafts treated with either NA or saline was 116.3 +/- 26.0 micrograms/liver (n = 4) or 5.7 +/- 2.2 micrograms (n = 4), respectively, while that of 350 donor islets was 29.4 +/- 2.5 micrograms (n = 5). The insulin content of the pancreas in the NA- or saline-treated recipients was 27.3 +/- 10.6 micrograms/pancreas (n = 4) or 2.7 +/- 1.2 micrograms (n = 4), respectively, while those of the pancreas from the diabetic rats without transplantation was 1.9 +/- 0.7 micrograms (n = 4) or 1.6 +/- 0.8 micrograms (n = 5), respectively. These findings clearly demonstrate that the hyperglycemia in the STZ-diabetic recipients after transplantation of an insufficient number of islets can be ameliorated while, in addition, the islet mass in the liver as well as the endogenous pancreas both increase in size with nicotinamide treatment.
本研究的目的是确定在经门静脉移植数量不足的同基因胰岛后，烟酰胺治疗能否改善链脲佐菌素（STZ）诱导的糖尿病大鼠的高血糖状态。WKA/Qdj（RT 1u）大鼠用作供体和受体。采用胶原酶技术分离胰岛。将总共350个胰岛通过门静脉移植到STZ诱导的糖尿病大鼠肝脏中。移植后60天，每天一次腹腔注射烟酰胺（NA，0.5 g/kg）或赋形剂（生理盐水）。所有未进行胰岛移植的糖尿病大鼠，无论是否接受NA治疗，均保持高血糖状态。所有接受胰岛移植并接受生理盐水治疗的受体（n = 12）在移植后60天仍保持高血糖（> 400 mg/dl）。与之形成显著对比的是，所有接受胰岛移植并接受NA治疗的受体（n = 18）在移植后16.2 +/- 7.1天（平均值 +/- 标准差）血糖恢复正常（< 200 mg/dl）。形态学上，在受体肝脏中很容易发现胰岛。醛复红染色显示，接受NA治疗的受体胰岛移植中的β细胞颗粒丰富，而接受生理盐水治疗的β细胞脱颗粒。接受NA或生理盐水治疗的移植肝脏的胰岛素含量分别为116.3 +/- 26.0微克/肝脏（n = 4）或5.7 +/- 2.2微克（n = 4），而350个供体胰岛的胰岛素含量为29.4 +/- 2.5微克（n = 5）。接受NA或生理盐水治疗的受体胰腺的胰岛素含量分别为27.3 +/- 10.6微克/胰腺（n = 4）或2.7 +/- 1.2微克（n = 4），而未移植的糖尿病大鼠胰腺的胰岛素含量分别为1.9 +/- 0.7微克（n = 4）或1.6 +/- 0.8微克（n = 5）。这些发现清楚地表明，移植数量不足的胰岛后，STZ糖尿病受体的高血糖状态可以得到改善，此外，烟酰胺治疗可使肝脏中的胰岛质量以及内源性胰腺的大小均增加。
