α/β-Hydrolase Domain Containing 5 Supports Glucose-Stimulated Lipolysis and Insulin Secretion in Pancreatic β-Cells.

Kim, Lucy; Liu, Siming; Peachee, Spencer; Richtsmeier, Syreine; Jun, Claudia; Sagona, Gianna; Vikram, Anamika; Freshly, Aidan et al. · Diabetes · 2026

basic_science · Level V

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Abstract

Lipolysis is stimulated by glucose and supports glucose-stimulated insulin secretion in pancreatic β-cells. However, the mechanism by which glucose increases lipolysis in β-cells is unknown. We aimed to identify a glucose-responsive regulator of lipolysis in β-cells. Glucose promotes α/β-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 β-cells affected by type 2 diabetes.