Research Paper Volume 15, Issue 20 pp 11152—11161
The novel GLP-1/GIP dual agonist DA3-CH improves rat type 2 diabetes through activating AMPK/ACC signaling pathway
- 1 Department of Endocrinology, Fuzhou Second Hospital, Fuzhou 350007, Fujian Province, China
- 2 The Third Clinical Medical College, Fujian Medical University, Fuzhou 362002, Fujian Province, China
- 3 Department of Internal Neurology, Fuzhou Second Hospital, Fuzhou 350007, Fujian Province, China
- 4 Department of Orthopedics Institute, Fuzhou Second Hospital, Fuzhou 350007, Fujian Province, China
Received: June 9, 2023 Accepted: September 26, 2023 Published: October 17, 2023
https://doi.org/10.18632/aging.205118How to Cite
Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.
Abbreviations
T2DM: Type 2 diabetes mellitus; GLP-1: glucagon like peptide-1; GIP: glucose dependent insulin stimulating polypeptide; AMPK: Adenylate activated protein kinase; ACC: acetyl CoA carboxylase; STZ: streptomycin; DMEM: Dulbecco’s modified Eagle medium; SPF: Specific pathogens free; Met: Metformin.