Iwase M, Nunoi K, Himeno H, Yoshinari M, Kikuchi M, Maki Y, Fujishima M
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Pancreas. 1994 May;9(3):344-8. doi: 10.1097/00006676-199405000-00010.
We studied the difference in the susceptibility to neonatal streptozotocin (STZ) diabetes between spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Two-day-old female SHR and WKY were injected intraperitoneally with 75.0 mg/kg of STZ or vehicle for control. Hyperglycemia developed in both strains at 4 days of age, but SHR were more hyperglycemic. Overt hyperglycemia developed in SHR with aging after a partial recovery from initial hyperglycemia at 10 days of age, whereas WKY did not develop significant hyperglycemia except shortly after STZ treatment. Percentage of insulin-positive B cells in total islet cells and pancreatic immunoreactive insulin (IRI) content were measured at 4 days, 10 days, 4 weeks, and 12 weeks of age. B cells per islet and pancreatic IRI content were significantly reduced in STZ-treated groups as compared with control in both SHR and WKY at 4 days of age, but later they increased significantly with aging in both strains. However, the reduction in pancreatic IRI content relative to control was significantly greater in SHR than in WKY from 4 days (-94.5 +/- 3.5%, -84.1 +/- 4.8%; p < 0.01) to 12 weeks (-97.1 +/- 2.1%, -28.0 +/- 2.5%; p < 0.05), and the reduction in B cells per islet was also greater in SHR at 4 weeks of age. These results indicated that the initial destruction of pancreatic B cells induced by STZ was greater, and the following regeneration was less in SHR than in WKY. The association of the susceptibility to neonatal STZ diabetes with the development of genetic hypertension in SHR remained to be elucidated.
我们研究了自发性高血压大鼠（SHR）和Wistar Kyoto大鼠（WKY）对新生期链脲佐菌素（STZ）诱导糖尿病易感性的差异。对2日龄雌性SHR和WKY腹腔注射75.0 mg/kg STZ或作为对照的赋形剂。两种品系在4日龄时均出现高血糖，但SHR的血糖更高。SHR在10日龄从初始高血糖部分恢复后随年龄增长出现明显高血糖，而WKY除在STZ治疗后不久外未出现明显高血糖。在4日龄、10日龄、4周龄和12周龄时测量胰岛细胞中胰岛素阳性B细胞的百分比和胰腺免疫反应性胰岛素（IRI）含量。在4日龄时，与对照组相比，STZ处理组的SHR和WKY中每个胰岛的B细胞和胰腺IRI含量均显著降低，但随后在两个品系中均随年龄显著增加。然而，从4日龄（-94.5±3.5%，-84.1±4.8%；p<0.01）到12周龄（-97.1±2.1%，-28.0±2.5%；p<0.05），SHR相对于对照组的胰腺IRI含量降低明显大于WKY，并且在4周龄时SHR中每个胰岛B细胞的减少也更大。这些结果表明，STZ诱导的胰腺B细胞初始破坏在SHR中更大，随后的再生在SHR中比在WKY中更少。SHR对新生期STZ糖尿病的易感性与遗传性高血压发展之间的关联仍有待阐明。
