Department of Endocrinology, Affiliated Ren He Hospital of China Three Gorges University, The Second Clinical Medical College of China Three Gorges University, Yichang, China.
Eur Rev Med Pharmacol Sci. 2021 Jul;25(14):4818-4828. doi: 10.26355/eurrev_202107_26395.
The purpose of this study was to explore the effect of liraglutide on pancreatic islet β cell apoptosis in rats with type 2 diabetes mellitus (T2DM) and the potential mechanisms.
SD rats were randomly divided into control group, model group, and liraglutide groups (200 and 100 μg/(kg·d)). Rats were fed with high sugar and high-fat diet for 8 weeks, and then streptozotocin (STZ) 40 mg/kg was intraperitoneally injected to establish T2DM model. After successful modeling, rats in the intervention group were given liraglutide through subcutaneous injection for 6 weeks. The indexes of glucose metabolism and lipid metabolism were measured. Apoptosis of islet β cells was detected by TUNEL. Western blot and RT-PCR were used to detect the protein and mRNA expression levels of IKK ε, NF-κ B, Bcl-2, Bax, IL-6, and Gal-3 in pancreatic tissue.
Compared with the control group, the serum FPG, INS, HOMA-IR, TC, TG, LDL-C, IL-6, islet apoptosis rate, glucagon, the positive expression rate of Gal-3, and body weight in the T2DM group were all significantly increased (p<0.05). However, the levels of insulin, SOD, HDL, and HOMA-β were notably decreased in the T2DM group in comparison with the control group (p<0.05). Moreover, the mRNA and protein expression levels of IKKε, NF-κB, Bax, IL-6, and Bax/Bcl-2 were markedly increased in pancreatic tissue (p<0.05). After liraglutide treatment, these changes were reversed in a dose-dependent manner.
Liraglutide improves pancreatic islet β cell apoptosis in rats with type 2 diabetes mellitus by inhibiting the IKKε/NF-κB pathway.
本研究旨在探讨利拉鲁肽对 2 型糖尿病（T2DM）大鼠胰岛β细胞凋亡的影响及其潜在机制。
SD 大鼠随机分为对照组、模型组和利拉鲁肽组（200 和 100μg/（kg·d））。大鼠给予高糖高脂饮食 8 周，然后腹腔注射链脲佐菌素（STZ）40mg/kg 建立 T2DM 模型。建模成功后，干预组大鼠给予利拉鲁肽皮下注射 6 周。测定糖脂代谢指标，TUNEL 法检测胰岛β细胞凋亡，Western blot 和 RT-PCR 法检测胰腺组织中 IKKε、NF-κB、Bcl-2、Bax、IL-6、Gal-3 的蛋白和 mRNA 表达水平。
与对照组比较，T2DM 组大鼠血清 FPG、INS、HOMA-IR、TC、TG、LDL-C、IL-6、胰岛凋亡率、胰高血糖素、Gal-3 阳性表达率及体重均显著升高（p<0.05），而胰岛素、SOD、HDL、HOMA-β 水平则显著降低（p<0.05）；此外，T2DM 组大鼠胰腺组织中 IKKε、NF-κB、Bax、IL-6、Bax/Bcl-2 的 mRNA 和蛋白表达水平均显著升高（p<0.05），经利拉鲁肽治疗后呈剂量依赖性降低。
利拉鲁肽通过抑制 IKKε/NF-κB 通路改善 2 型糖尿病大鼠胰岛β细胞凋亡。
