Liraglutide improves pancreatic islet β cell apoptosis in rats with type 2 diabetes mellitus by inhibiting the IKKε/NF-κB pathway

Y.-T. Liu, T. He, H.-Q. Li, P. Jiang

Department of Endocrinology, Affiliated Ren He Hospital of China Three Gorges University, The Second Clinical Medical College of China Three Gorges University, Yichang, China. huiqiongli@yeah.net

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• Pharmacology

OBJECTIVE: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: Liraglutide improves pancreatic islet β cell apoptosis in rats with type 2 diabetes mellitus by inhibiting the IKKε/NF-κB pathway.

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