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GLIMEPIRIDE-INDUCED PREVENTION OF DIABETES AND AUTOIMMUNE EVENTS IN THE BB RAT - REVISED

机译：格列吡脲诱导的BB鼠糖尿病和自身免疫性疾病的预防-修订版

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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 50-100 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. [References: 21]
机译：这项研究的目的是确定格列美脲（一种口服磺酰脲类药物）是否可以预防糖尿病易感BB大鼠的糖尿病发作。还测试了具有最小的体内葡萄糖代谢作用的磺酰脲类药物S750181。另外，确定了预防所需的最短磺酰脲治疗时间。研究了80只大鼠的所有治疗期，其中40只接受每日口服管饲格列美脲和40只接受每日口服管饲剂的媒介物溶液。通过糖尿和血糖水平监测糖尿病的发作。在研究I中，治疗期为35-142天，格列美脲治疗的大鼠的糖尿病发生率为32％，而对照大鼠的糖尿病发生率为55％（p <0.04）。在研究II中，治疗期为60-140天，格列美脲治疗的大鼠患糖尿病的发生率为29％，而对照组为54％（p <0.03）。此外，比较格列美脲和对照组之间糖尿病的发作时间显示格列美脲可延迟糖尿病的发作（p <0.02）。在研究III中，使用50至100天的治疗期，格列美脲治疗的大鼠在170天时显示出17％的总体糖尿病发生率，而对照组为43％（p <0.01）。在研究IV中，治疗期为60-140天，S750181治疗的大鼠显示38％的糖尿病发生率，对照组显示43％的糖尿病发生率。在S750181组中没有观察到明显的延迟或预防作用。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性。在研究I中，来自全部和非糖尿病动物的胰岛组织学表明，格列美脲治疗的大鼠的胰岛炎症严重程度低于对照组（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天的较短治疗时间有效，并且c）格列美脲可降低胰岛炎症的严重性。 [参考：21]

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