新型 GLP-1/GIP 双重激动剂 DA3-CH 通过激活 AMPK/ACC 信号通路改善大鼠 2 型糖尿病。
The novel GLP-1/GIP dual agonist DA3-CH improves rat type 2 diabetes through activating AMPK/ACC signaling pathway.
机构信息
Department of Endocrinology, Fuzhou Second Hospital, Fuzhou 350007, Fujian Province, China.
The Third Clinical Medical College, Fujian Medical University, Fuzhou 362002, Fujian Province, China.
出版信息
Aging (Albany NY). 2023 Oct 17;15(20):11152-11161. doi: 10.18632/aging.205118.
BACKGROUND
Type 2 diabetes mellitus (T2DM) accounts for more than 95% of all diabetes. DA3-CH is a novel dual receptor agonist of glucagon like peptide-1 (GLP-1) and glucose dependent insulin stimulating polypeptide (GIP). The regulatory role of DA3-CH in T2DM has not been reported.
METHODS
T2DM rat model was established successfully with high sugar and fat feed and streptomycin (STZ) induction. The mRNA and protein expression were measured with RT-PCR and western blotting. The apoptosis level in the pancreatic tissue was evaluated with Tunel staining. Blood glucose, fat, and oxidative stress indicators were measured.
RESULTS
DA3-CH greatly improved T2DM symptoms by reducing blood glucose, blood fat, pancreatic tissue injury, apoptosis, and oxidative stress condition. The inactivation of Adenylate activated protein kinase (AMPK)/acetyl CoA carboxylase (ACC) signaling pathway in T2DM rats was promoted by DA3-CH. The influence of DA3-CH was significantly reversed by Com-C, the inhibitor of AMPK/ACC signaling pathway.
CONCLUSIONS
DA3-CH might improve T2DM through targeting AMPK/ACC signaling pathway. This study might provide a novel therapeutic strategy for the prevention and treatment of T2DM through targeting DA3-CH and AMPK/ACC signaling pathway.
背景
2 型糖尿病（T2DM）占所有糖尿病的 95%以上。DA3-CH 是胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性胰岛素刺激多肽（GIP）的新型双重受体激动剂。DA3-CH 在 T2DM 中的调节作用尚未报道。
方法
采用高糖高脂饲料联合链脲佐菌素（STZ）诱导成功建立 T2DM 大鼠模型。采用 RT-PCR 和 Western blot 检测 mRNA 和蛋白表达。Tunel 染色评估胰腺组织中的细胞凋亡水平。检测血糖、血脂和氧化应激指标。
结果
DA3-CH 通过降低血糖、血脂、胰腺组织损伤、细胞凋亡和氧化应激状态，显著改善 T2DM 症状。DA3-CH 促进 T2DM 大鼠腺苷酸激活蛋白激酶（AMPK）/乙酰辅酶 A 羧化酶（ACC）信号通路失活。AMPK/ACC 信号通路抑制剂 Com-C 显著逆转了 DA3-CH 的影响。
结论
DA3-CH 可能通过靶向 AMPK/ACC 信号通路改善 T2DM。本研究为通过靶向 DA3-CH 和 AMPK/ACC 信号通路预防和治疗 T2DM 提供了一种新的治疗策略。
Zotero 插件