Long-term pharmacokinetic and pharmacological evaluations of a novel indole-benzazepinone derivative on obese Type 2 diabetes mellitus

Author:

Wang Youde1ORCID,Li Shuai1,Yan Zhiwei1,Guo Yachun2,Yang Dongxin1,Zhang Liying1

Affiliation:

1. Key Laboratory of Traditional Chinese Medicine Research & Development of Hebei Province, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde, 067000, China

2. Department of Pathogen Biology, Chengde Medical University, Chengde, 067000, Hebei, China

Abstract

Background: Owing to the chronic nature of Type 2 diabetes mellitus, antidiabetic drugs must have long-lasting efficacy. Compound 1 has a good inhibitory effect on acute hyperglycemia, but its long-term hypoglycemic effect has not been evaluated. Results: Preliminary prediction and in vitro experimental pharmacokinetic results support the use of compound 1 for long-term in vivo experiments. Long-term experiments demonstrated that compound 1 significantly reduces blood glucose, improves the oral glucose tolerance of obese mice and has a positive effect on body weight, free fatty acid, hepatocyte steatosis and inflammatory cell infiltration. Conclusion: These findings lay a good foundation for the further exploration and development of novel glycogen phosphorylase inhibitors.

Funder

Natural Science Foundation of Hebei Province

Hebei Province Key Laboratory of Traditional Chinese Medicine Research and Development

Technology Innovation Guidance Project–Science and Technology Work Conference Fund of Hebei Provincial Department of Science and Technology

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

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