Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa 13133, Jordan.
Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa 13133, Jordan.
Cells. 2023 Jan 9;12(2):267. doi: 10.3390/cells12020267.
2',3,3,5'-Tetramethyl-4'-nitro-2'H-1,3'-bipyrazole (TMNB) is a novel bipyrazole compound with unknown therapeutic potential in diabetes mellitus. This study aims to investigate the anti-diabetic effects of TMNB in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with TMNB (10 mg/kg) or (200 mg/kg) metformin for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. TMNB reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group ( 0.001). TMNB abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats ( 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with TMNB compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 and AMPK were upregulated following treatment with TMNB ( 0.001, < 0.01, respectively). TMNB was able to upregulate GLUT2 and AMPK protein expression in liver ( < 0.001, < 0.001, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with TMNB compared to the vehicle controls ( < 0.001, 0.01, respectively). TMNB reduced MDA and IL-6 levels ( < 0.001), and increased GSH level ( < 0.05) in diabetic rats compared to the vehicle controls. Conclusion: TMNB ameliorates insulin resistance, oxidative stress, and inflammation in a T2D model. TMNB could represent a promising therapeutic agent to treat T2D.
2',3,3,5'-四甲基-4'-硝基-2'H-1,3'-联吡唑（TMNB）是一种新型联吡唑化合物，在糖尿病中具有未知的治疗潜力。本研究旨在研究 TMNB 在高脂肪饮食和链脲佐菌素（HFD/STZ）诱导的 2 型糖尿病（T2D）大鼠模型中的抗糖尿病作用。大鼠喂食 HFD，然后单次给予低剂量 STZ（40mg/kg）。HFD/STZ 糖尿病大鼠在实验结束前用 TMNB（10mg/kg）或（200mg/kg）二甲双胍口服治疗 10 天，并收集血浆、比目鱼肌、脂肪组织和肝脏进行进一步下游分析。与载体对照组相比，TMNB 降低了糖尿病大鼠升高的血清葡萄糖水平（ 0.001）。与载体对照大鼠相比，TMNB 消除了治疗组糖尿病大鼠血清胰岛素的增加（ 0.001）。与载体对照组相比，TMNB 治疗的糖尿病大鼠的胰岛素抵抗稳态模型评估（HOMA-IR）降低。TMNB 处理后骨骼肌和脂肪组织 GLUT4 和 AMPK 蛋白含量上调（ 0.001，<0.01，分别）。TMNB 能够上调肝中 GLUT2 和 AMPK 蛋白表达（<0.001，<0.001，分别）。与载体对照组相比，TMNB 治疗的糖尿病大鼠的 LDL、甘油三酯和胆固醇降低（<0.001，0.01，分别）。与载体对照组相比，TMNB 降低了糖尿病大鼠的 MDA 和 IL-6 水平（<0.001），并增加了 GSH 水平（<0.05）。结论：TMNB 改善了 T2D 模型中的胰岛素抵抗、氧化应激和炎症。TMNB 可能成为治疗 T2D 的有前途的治疗剂。
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