Abstract <p>Hyperactivated ABCC8 is associated with defective insulin secretion and maturity-onset diabetes of the young (MODY). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used in the treatment of type 2 diabetes. However, the therapeutic effects of GLP-1 RAs on diabetes associated with activated ABCC8 remain incompletely understood. In this study, we established pancreatic MIN6 cells with stable overexpression of wild-type and mutant ABCC8 (activating form). Subsequently, we assessed the proliferation, insulin, and C-peptide secretion of these MIN6 cells. The impact of a GLP-1 RA, liraglutide, on the proliferation and secretory function of MIN6 cells and pancreatic β-cells in diabetic mice expressing mutant ABCC8 was also investigated. Our findings indicate that MIN6 cells overexpressing wild-type ABCC8 exhibited increased insulin and C-peptide secretion, while those expressing mutant ABCC8 showed comparable levels to that of control cells. Consistently, in fasting diabetic mice, overexpression of wild-type ABCC8 elevated insulin and C-peptide secretion, while overexpression of mutant ABCC8 had no such effect. Notably, treatment with liraglutide stimulated the proliferation and secretory function of MIN6 cells and pancreatic β-cells in diabetic mice overexpressing mutant ABCC8. These findings suggest that GLP-1 RA holds promise as a therapeutic option for diabetes caused by ABCC8 hyperactivation.</p>