Abstract
Adipose Triglyceride Lipase is a Key Lipase for the Mobilization of Lipid Droplets in Human Beta Cells and Critical for the Maintenance of Syntaxin1a Level in Beta Cells
Diabetes (New York, N.Y.), p.db190951
03/31/2020
DOI: 10.2337/db09-0951
PMID: 32234723
Abstract
Lipid droplets (LDs) are frequently increased when excessive lipid accumulation leads to cellular dysfunction. Distinct from mouse beta cells, LDs are prominent in human beta cells, however, the regulation of LD mobilization (lipolysis) in human beta cells remains unclear. We found that glucose increases lipolysis in non-diabetic human islets, but not in type 2 diabetic (T2D) islets, indicating dysregulation of lipolysis in T2D islets. Silencing adipose triglyceride lipase (ATGL) in human pseudoislets (shATGL) increased triglycerides, and the number and size of LDs indicating that ATGL is the principal lipase in human beta cells. In shATGL pseudoislets, biphasic glucose-stimulated insulin secretion (GSIS) and insulin secretion to IBMX and KCl were all reduced without altering oxygen consumption rate compared with scramble control. Like human islets, INS1 cells showed visible LDs, glucose responsive lipolysis, and impairment of GSIS after ATGL silencing. ATGL deficient INS1 cells and human pseudoislets showed reduced Stx1a, a key SNARE component. Proteasomal degradation of Stx1a was accelerated likely through reduced palmitoylation in ATGL deficient INS1 cells. Therefore, ATGL is responsible for LD mobilization in human beta cells and supports insulin secretion by stabilizing Stx1a. The dysregulated lipolysis may contribute to LD accumulation and beta cell dysfunction in T2D islets.
Details
- Title: Subtitle
- Adipose Triglyceride Lipase is a Key Lipase for the Mobilization of Lipid Droplets in Human Beta Cells and Critical for the Maintenance of Syntaxin1a Level in Beta Cells
- Creators
- Siming Liu - University of IowaJoseph A Promes - University of IowaMikako Harata - Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IowaAkansha Mishra - University of IowaSamuel B Stephens - University of IowaEric B Taylor - University of IowaAnthony J Burand Jr - Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, IowaWilliam I Sivitz - University of IowaBrian D Fink - University of IowaJames A Ankrum - University of IowaYumi Imai - Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa
- Resource Type
- Abstract
- Publication Details
- Diabetes (New York, N.Y.), p.db190951
- DOI
- 10.2337/db09-0951
- PMID
- 32234723
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Grant note
- P30 DK054759 / NIDDK NIH HHS
- Language
- English
- Date published
- 03/31/2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984363447002771
Metrics
37 Record Views