Shimazoe T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Nihon Yakurigaku Zasshi. 2000 Aug;116(2):71-8. doi: 10.1254/fpj.116.71.
The biological clock mechanism was studied in both non-insulin-dependent and insulin-dependent diabetic model rats. Otsuka Long Evans Tokushima Fatty (OLETF) rats were used as a non-insulin-dependent model. Streptozotocin (STZ, 100 mg/kg, i.p.) was administered to 8- to 10-week-old Wistar rats for an insulin-dependent diabetic model. Both young non-diabetic OLETF and STZ-induced diabetic rats needed more days for re-entrainment to a new light-dark cycle than control rats on activity rhythm. In young OLETF rats, dim-light-induced Fos expression (50 and 100 lux) was significantly decreased in the suprachiasmatic nucleus. In diabetic OLETF rats, Fos expression was decreased by the exposure of light at 300 lux. In STZ-induced diabetic rats, Fos expression was also decreased by 300 lux of light. In OLETF rats, the phase delay by glutamate application was significantly smaller than that in control rats on the suprachiasmatic nucleus neuronal (SCN) activity rhythms. On the other hand, the same level of phase delay was observed between control and STZ-induced diabetic rats by glutamate application. These results suggest that entrainment function is disordered in OLETF rats before the onset of hyperglycemia. To clarify the entrainment function of STZ-induced diabetic rats, however, further study is necessary.
在非胰岛素依赖型和胰岛素依赖型糖尿病模型大鼠中研究了生物钟机制。将大冢长-伊万里-德岛肥胖(OLETF)大鼠用作非胰岛素依赖型模型。给8至10周龄的Wistar大鼠腹腔注射链脲佐菌素(STZ,100 mg/kg)以建立胰岛素依赖型糖尿病模型。在活动节律方面,年轻的非糖尿病OLETF大鼠和STZ诱导的糖尿病大鼠重新适应新的明暗周期所需的天数均比对照大鼠多。在年轻的OLETF大鼠中,暗光诱导的视交叉上核Fos表达(50和100勒克斯)显著降低。在糖尿病OLETF大鼠中,300勒克斯光照可使Fos表达降低。在STZ诱导的糖尿病大鼠中,300勒克斯光照也可使Fos表达降低。在OLETF大鼠中,视交叉上核神经元(SCN)活动节律方面,谷氨酸应用引起的相位延迟显著小于对照大鼠。另一方面,在对照大鼠和STZ诱导的糖尿病大鼠中,谷氨酸应用引起的相位延迟水平相同。这些结果表明,在高血糖症发作之前,OLETF大鼠的昼夜节律调节功能紊乱。然而,为了阐明STZ诱导的糖尿病大鼠的昼夜节律调节功能,还需要进一步研究。