Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Diabetes. 2013 Dec;5(4):421-8. doi: 10.1111/1753-0407.12061. Epub 2013 Jun 4.
Glucagon-like peptide-1 (GLP-1) analogues have emerged as insulin secretagogues and are widely used in type 2 diabetic patients. GLP-1 analogues also demonstrate a promotion of beta cell proliferation and reduction of apoptosis in rodents. In the present study, we investigated the protection of pancreatic beta cells by early use (at the age of 2 weeks) of GLP-1 analogue, liraglutide in Gato-Kakizaki (GK) rats and explored the underlying mechanisms.
The effects of liraglutide on glucose tolerance were evaluated by intraperitoneal glucose tolerance test (IPGTT) and insulin release tests (IRT). Ki67 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) immunostaining, Western blots and real-time polymerase chain reaction were applied to evaluate cell proliferation, apoptosis and related gene expressions.
Our results demonstrated that early use of liraglutide improved glucose tolerance during liraglutide treatment in GK rats. Liraglutide increased pancreatic insulin contents and markedly reduced beta cell apoptosis. Liraglutide also downregulated pro-apoptotic gene expressions and reduced intra-islet macrophage infiltration.
This experiment reported for the first time that early use of liraglutide could protect beta cell failure in pre-diabetic GK rats through reduction of beta cell apoptosis and ameliorating islet inflammation.
胰高血糖素样肽-1（GLP-1）类似物已成为胰岛素促分泌剂，广泛应用于 2 型糖尿病患者。GLP-1 类似物还能促进啮齿动物β细胞增殖，减少细胞凋亡。在本研究中，我们研究了在 Gato-Kakizaki（GK）大鼠中早期使用 GLP-1 类似物利拉鲁肽对胰岛β细胞的保护作用，并探讨了其潜在机制。
通过腹腔内葡萄糖耐量试验（IPGTT）和胰岛素释放试验（IRT）评估利拉鲁肽对葡萄糖耐量的影响。Ki67 和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）免疫染色、Western blot 和实时聚合酶链反应用于评估细胞增殖、细胞凋亡和相关基因表达。
我们的结果表明，在 GK 大鼠中，早期使用利拉鲁肽可改善利拉鲁肽治疗期间的葡萄糖耐量。利拉鲁肽增加了胰腺胰岛素含量，并显著减少了β细胞凋亡。利拉鲁肽还下调了促凋亡基因的表达，并减少了胰岛内巨噬细胞浸润。
本实验首次报道，早期使用利拉鲁肽可通过减少β细胞凋亡和改善胰岛炎症来保护糖尿病前期 GK 大鼠的β细胞衰竭。
