维尔达格利普汀
内分泌学
内科学
二肽基肽酶-4
小岛
二肽基肽酶
肠内分泌细胞
医学
脂肪变性
糖尿病
激素
2型糖尿病
胰高血糖素样肽-1
饮食性肥胖
胰岛素
化学
胰岛素抵抗
内分泌系统
酶
生物化学
作者
Lei Fan,Hee‐Young Yang,Xiaolong Hu,Juncheng Liu,Yuehua You,Xinyu Li,Guangcheng Qin,Qian Ge,Yi Hou,Xiaoqiu Xiao
出处
期刊:Life Sciences
[Elsevier]
日期:2022-06-01
卷期号:298: 120515-120515
标识
DOI:10.1016/j.lfs.2022.120515
摘要
Dipeptidyl peptidase-4 (DPP-4) inhibitors have been extensively used for the treatment of type 2 diabetes mellitus. Nevertheless, side effects like sore throat and diarrhea also occur in DPP-4 inhibitors treatment. The study aims to identify and develop novel DPP-4 inhibitors with better therapeutic profiles.Here we synthesized a series of vildagliptin analogs, and among which, ZD-2 showed the moderate inhibition of DPP-4 activity compared with vildagliptin. High-fat-diet (HFD) mice were treated with ZD-2 (4.5 and 7.5 mg/kg) or vildagliptin (6 mg/kg) for 7 weeks following the examinations of metabolic index and pancreatic β-cell function. Mouse pancreatic cell line MIN6 was used to evaluate β-cell function, and intestinal enteroendocrine cell line STC-1 was used to evaluate the expression of gut hormones.The IC50 of ZD-2 was over 30-fold higher than vildagliptin. However, both ZD-2 and vildagliptin treatment showed comparable effects on improving glucose tolerance and reducing the steatosis of liver and fat mass in HFD mice. Moreover, ZD-2 exerted β-cell-protective actions by preserving islet β-cell mass and increasing the expression of functional β-cell-related genes. Additionally, ZD-2 also stimulated the expression of gut hormones in STC-1 cells.ZD-2 showed comparable anti-diabetic activities in HFD-fed mice although its lower potency on inhibition of DPP-4 compared with vildagliptin. Protection of β-cell function might contribute to its anti-diabetic effects.
科研通智能强力驱动
Strongly Powered by AbleSci AI