Cheta D M, Lim J, Chan E K, Kunakorn T, Charles M A
University of California, Department of Medicine, Irvine 92717-4065, USA.
Life Sci. 1995;57(24):2281-90. doi: 10.1016/0024-3205(95)02221-4.
The purpose of this study was to determine whether Glimepiride, an oral sulfonylurea drug, prevents the onset of diabetes in diabetic prone BB rats. S750181, a sulfonylurea drug that has minimal in vivo glucose metabolic effects, was also tested. In addition, the shortest period of sulfonylurea treatment required for prevention was determined. Eighty rats were studied for all treatment periods with 40 receiving a daily oral gavage dosage of glimepiride and 40 receiving a daily oral gavage dosage of vehicle solution. Diabetes onset was monitored by glycosuria and blood glucose levels. In study I, with a treatment period of 35-142 days of age, Glimepiride-treated rats showed a 32% incidence of diabetes, whereas control rats had a diabetes incidence of 55% (p < 0.04). In study II, with a treatment period of 60-140 days of age, Glimepiride-treated rats showed a 29% incidence of diabetes compared to 54% in controls (p < 0.03). Further, comparing the time of diabetes onset between the Glimepiride and control groups showed that Glimepiride delays diabetes onset (p < 0.02). In study III, with a treatment period of 60-100 days of age, Glimepiride-treated rats showed a 17% overall diabetes incidence at 170 days, whereas the controls were 43% (p < 0.01). In study IV, with a treatment period of 60-140 days of age, S750181-treated rats showed a 38% diabetes incidence and the control group showed a 43% diabetes incidence. There was no significant delaying or prevention effect observed in the S750181 group. To determine if Glimepiride affected autoimmune events, the severity of islet inflammation was examined. In study I, islet histology from total and nondiabetic animals indicated that Glimepiride-treated rats had a lower severity of islet inflammation than that of the control rats (p = 0.023). These studies show that a) Glimepiride has diabetes preventive effects, b) shorter treatment periods of only 40 days can be effective and c) Glimepiride decreases the severity of islet inflammation.
本研究的目的是确定口服磺脲类药物格列美脲是否能预防糖尿病倾向的BB大鼠患糖尿病。还对体内葡萄糖代谢作用极小的磺脲类药物S750181进行了测试。此外，还确定了预防所需的最短磺脲类药物治疗期。对80只大鼠进行了所有治疗期的研究，其中40只每日经口灌胃给予格列美脲，40只每日经口灌胃给予赋形剂溶液。通过糖尿和血糖水平监测糖尿病的发病情况。在研究I中，治疗期为35 - 142日龄，格列美脲治疗组大鼠的糖尿病发病率为32%，而对照组大鼠的糖尿病发病率为55%（p < 0.04）。在研究II中，治疗期为60 - 140日龄，格列美脲治疗组大鼠的糖尿病发病率为29%，而对照组为54%（p < 0.03）。此外，比较格列美脲组和对照组之间的糖尿病发病时间表明，格列美脲可延迟糖尿病发病（p < 0.02）。在研究III中，治疗期为60 - 100日龄，格列美脲治疗组大鼠在170日时的总体糖尿病发病率为17%，而对照组为43%（p < 0.01）。在研究IV中，治疗期为60 - 140日龄，S750181治疗组大鼠的糖尿病发病率为38%，对照组为43%。在S750181组中未观察到显著的延迟或预防作用。为了确定格列美脲是否影响自身免疫事件，检查了胰岛炎症的严重程度。在研究I中，来自全部和非糖尿病动物的胰岛组织学表明，格列美脲治疗组大鼠的胰岛炎症严重程度低于对照组大鼠（p = 0.023）。这些研究表明：a）格列美脲具有预防糖尿病的作用；b）仅40天的较短治疗期即可有效；c）格列美脲可降低胰岛炎症的严重程度。
