Koh G, Seino Y, Usami M, Matsuo T, Ikeda H, Yamamoto T, Tsuda K, Taminato T, Imura H
Division of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, Japan.
Diabetes. 1990 Sep;39(9):1050-6. doi: 10.2337/diab.39.9.1050.
To investigate the role of the beta-cell in the occurrence of diabetes in obesity, longitudinal changes of insulin-gene expression and pancreatic insulin content were compared among genetically obese diabetic (Wistar fatty) rats, genetically obese nondiabetic (Zucker fatty) rats, and ventromedial hypothalamus (VMH)-lesioned obese rats. Plasma glucose levels were significantly elevated with age in Wistar fatty rats, whereas they were virtually unchanged in VMH-lesioned and Zucker fatty rats. Obesity and hyperinsulinemia were evident in VMH-lesioned rats 1 wk after the operation and in Zucker and Wistar fatty rats at 5 wk of age. In VMH-lesioned rats, the pancreatic preproinsulin I mRNA (pplmRNA) level and pancreatic insulin content markedly increased approximately two- to threefold (P less than 0.001) with the development of hyperinsulinemia, whereas sham-operated rats showed no significant change. In Zucker and Wistar lean rats, the pplmRNA level and pancreatic insulin content increased with age, corresponding to increases in body weight. In Zucker fatty rats, the pplmRNA level and pancreatic insulin content at 5 and 14 wk of age were significantly higher than those of lean littermates. The pplmRNA level in Zucker fatty rats at 14 wk of age reached 290% of that of their lean littermates (P less than 0.001). On the other hand, the pplmRNA level and pancreatic insulin content in Wistar fatty rats at 5 and 14 wk of age did not increase more than those of their lean littermates at the corresponding ages and were therefore significantly lower than in Zucker fatty rats, which had a higher grade of hyperinsulinemia at 14 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS)
为研究β细胞在肥胖相关性糖尿病发生中的作用，我们比较了遗传性肥胖糖尿病（Wistar肥胖）大鼠、遗传性肥胖非糖尿病（Zucker肥胖）大鼠以及腹内侧下丘脑（VMH）损伤的肥胖大鼠胰岛素基因表达和胰腺胰岛素含量的纵向变化。Wistar肥胖大鼠的血糖水平随年龄显著升高，而VMH损伤大鼠和Zucker肥胖大鼠的血糖水平基本未变。VMH损伤大鼠在术后1周、Zucker和Wistar肥胖大鼠在5周龄时出现肥胖和高胰岛素血症。在VMH损伤大鼠中，随着高胰岛素血症的发展，胰腺前胰岛素原I mRNA（pplmRNA）水平和胰腺胰岛素含量显著增加约2至3倍（P<0.001），而假手术大鼠无显著变化。在Zucker和Wistar瘦大鼠中，pplmRNA水平和胰腺胰岛素含量随年龄增加，与体重增加相对应。在Zucker肥胖大鼠中，5周龄和14周龄时的pplmRNA水平和胰腺胰岛素含量显著高于同窝瘦鼠。Zucker肥胖大鼠14周龄时的pplmRNA水平达到同窝瘦鼠的290%（P<0.001）。另一方面，Wistar肥胖大鼠5周龄和14周龄时的pplmRNA水平和胰腺胰岛素含量相比相应年龄的同窝瘦鼠增加不多，因此显著低于14周龄时高胰岛素血症程度更高的Zucker肥胖大鼠。（摘要截断于250字）
