Exenatide regulates Th17/Treg balance via PI3K/Akt/FoxO1 pathway in db/db mice

• DOI: 10.1186/s10020-022-00574-6
• Publication Date: 2022-12-03T06:03:21Z
• Authors: Qinqin Xu; Xiaoling Zhang; Tao Li; Shiying Shao
• Keywords: FOXO1; Insulitis

Abstract Background The T helper 17 (Th17)/T regulatory (Treg) cell imbalance is involved in the course of obesity and type 2 diabetes mellitus (T2DM). In current study, exact role glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide on regulating Th17/Treg balance underlying molecular mechanisms are investigated obese diabetic mice model. Methods Metabolic parameters were monitored db/db treated with/without during 8-week study period. frequencies Th17 Treg cells from peripheral blood pancreas assessed. phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Forkhead box O1 (FoxO1) pathway spleens male C57BL/6J was detected by western blotting. addition, expression (GLP-1R) mononuclear (PBMCs) analyzed. Results Exenatide treatment improved β-cell function insulitis addition to glucose, insulin sensitivity weight. Increased decreased present as progressed while corrected this imbalance. Progressive IL-17 + infiltration pancreatic islets alleviated intervention. vitro showed no significant difference level GLP-1R PBMCs between control palmitate (PA) groups. PA could promote but suppress differentiation along with down-regulating phosphorylation PI3K/Akt/FoxO1, which reversed FoxO1 inhibitor AS1842856 abrogate all these effects against lipid stress. Conclusions restore systemic via progression mice. protection may be partially mediated inhibiting into islets, resultant alleviation islet inflammation.