Journal article
α/β-Hydrolase Domain Containing 5 Supports Glucose-Stimulated Lipolysis and Insulin Secretion in Pancreatic β-Cells
Diabetes (New York, N.Y.), Vol.75(8), pp.1411-1423
08/2026
DOI: 10.2337/db25-1156
PMID: 42207953
Abstract
Adipose triglyceride (TG) lipase (ATGL) is the rate-limiting enzyme of TG catabolism at the surface of lipid droplets (LDs). In pancreatic β-cells, lipolysis by ATGL increases with glucose and produces metabolites that support glucose-stimulated insulin secretion (GSIS). Upregulation of lipolysis by glucose is blunted in human islets affected by type 2 diabetes. However, how glucose regulates lipolysis in β-cells is unknown. We found that glucose recruits ATGL coactivator α/β-hydrolase domain containing 5 (ABHD5) to LDs in INS-1 cells and human β-cells. ABHD5 recruitment to LDs was reduced by inhibitors of cAMP-dependent kinase (PKA) or the expression of PKA-resistant mutant ABHD5, indicating that PKA phosphorylation contributes to ABHD5 recruitment to LDs. Importantly, ABHD5 was indispensable for glucose-stimulated lipolysis in INS-1 cells and human β-cells. ABHD5 knockdown increased LDs and TG content in INS-1 cells and human islets, indicating that ABHD5 is a critical regulator of ATGL activity in β-cells. Additionally, GSIS was impaired in ABHD5-downregulated INS-1 cells and human pseudoislets, which agrees with a role of ATGL in supporting GSIS in β cells. Thus, ABHD5 plays an important role in conferring glucose responsiveness in lipolysis and supporting insulin secretion in β-cells.
Details
- Title: Subtitle
- α/β-Hydrolase Domain Containing 5 Supports Glucose-Stimulated Lipolysis and Insulin Secretion in Pancreatic β-Cells
- Creators
- Lucy Kim - University of IowaSiming Liu - University of IowaSpencer Peachee - University of IowaSyreine Richtsmeier - University of IowaClaudia Jun - University of IowaGianna Sagona - University of IowaAnamika Vikram - University of IowaAidan Freshly - University of IowaFarakh Haider - University of IowaYumi Imai - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.75(8), pp.1411-1423
- DOI
- 10.2337/db25-1156
- PMID
- 42207953
- NLM abbreviation
- Diabetes
- ISSN
- 1939-327X
- eISSN
- 1939-327X
- Publisher
- American Diabetes Association
- Grant note
- I01 BX005107 / BLRD VA R01DK090490 / NIDDK NIH HHS 2UC4DK098085 / NIDDK NIH HHS
- Language
- English
- Electronic publication date
- 05/28/2026
- Date published
- 08/2026
- Academic Unit
- Neurology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9985166962802771
Metrics
6 Record Views