Kim_2026_Diabetes__db251156

Lipolysis is stimulated by glucose and supports glucose-stimulated insulin secretion in pancreatic beta-cells. However, the mechanism by which glucose increases lipolysis in beta-cells is unknown. We aimed to identify a glucose-responsive regulator of lipolysis in beta-cells. Glucose promotes alpha/beta-hydrolase domain containing 5 (ABHD5) recruitment to lipid droplets where lipolysis occurs, which is at least partially mediated by cAMP-dependent kinase A. ABHD5 is required for glucose-stimulated lipolysis and insulin secretion. ABHD5 is a potential target to restore glucose-stimulated lipolysis in beta-cells affected by type 2 diabetes.