BACKGROUND The study aimed to investigate whether timolol-treatment has a beneficial effect on pentose phosphate pathway enzyme activities such as glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGDH) enzyme activities and cAMP level in streptozotocin-induced diabetic rats in pancreatic tissues. METHODS Diabetes was induced by streptozotocin (STZ) in 3-month old male Wistar rats. The diabetic rats were treated with timolol (5 mg/kg body weight, for 12 weeks) while the control group received saline. Enzyme activities were determined in pancreas tissue. To support our results, we performed in silico calculations, using Protein Data Bank structures. RESULTS Timolol treatment of STZ-induced diabetic rats had no noteworthy effect on high blood-glucose levels. However, this treatment induced activities of G6PD and 6PGDH in diabetic rats. Timolol treatment significantly increased cAMP level in diabetic pancreatic tissue. We found that timolol cannot bind strongly to either G6PD or 6PGD, but there is a relatively higher binding affinity to adenylyl cyclase, responsible for cAMP production, serving as a regulatory signal via specific cAMP-binding proteins. CONCLUSIONS Our data point out that timolol treatment has beneficial effects on the antioxidant defence mechanism enzymes in the pancreas of STZ-induced diabetic rats.

中文翻译：

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噻吗洛尔治疗对链脲佐菌素诱导的糖尿病大鼠胰腺抗氧化酶的影响：实验和计算研究。

背景本研究旨在探讨噻吗洛尔治疗是否对链脲佐菌素诱导的糖尿病大鼠的戊糖磷酸途径酶活性（例如葡萄糖-6-磷酸脱氢酶（G6PD）、6-磷酸葡萄糖酸脱氢酶（6PGDH）酶活性和cAMP水平）具有有益影响在胰腺组织中。方法用链脲佐菌素（STZ）在3个月大的雄性Wistar大鼠中诱导糖尿病。糖尿病大鼠接受噻吗洛尔治疗（5 mg/kg 体重，持续 12 周），而对照组则接受生理盐水治疗。测定胰腺组织中的酶活性。为了支持我们的结果，我们使用蛋白质数据库结构进行了计算机计算。结果噻吗洛尔治疗STZ诱导的糖尿病大鼠对高血糖水平没有显着影响。然而，这种治疗会诱导糖尿病大鼠体内 G6PD 和 6PGDH 的活性。噻吗洛尔治疗显着增加糖尿病胰腺组织中的 cAMP 水平。我们发现噻吗洛尔不能与 G6PD 或 6PGD 强烈结合，但与腺苷酸环化酶有相对较高的结合亲和力，腺苷酸环化酶负责 cAMP 的产生，通过特定的 cAMP 结合蛋白作为调节信号。结论 我们的数据表明，噻吗洛尔治疗对 STZ 诱导的糖尿病大鼠胰腺中的抗氧化防御机制酶具有有益作用。