Lipid Droplets Protect Human β-Cells From Lipotoxicity-Induced Stress and Cell Identity Changes.
Calcium
Cell Differentiation
Cell Line
Diabetes Mellitus, Type 2
/ metabolism
Glucose
/ pharmacology
Homeostasis
Humans
Insulin Secretion
/ drug effects
Insulin-Secreting Cells
/ metabolism
Lipid Droplets
/ metabolism
Lipid Metabolism
Lipids
/ toxicity
Perilipin-2
/ genetics
RNA, Messenger
/ genetics
Stress, Physiological
Journal
Diabetes
ISSN: 1939-327X
Titre abrégé: Diabetes
Pays: United States
ID NLM: 0372763
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
26
03
2021
accepted:
19
08
2021
pubmed:
27
8
2021
medline:
30
12
2021
entrez:
26
8
2021
Statut:
ppublish
Résumé
Free fatty acids (FFAs) are often stored in lipid droplet (LD) depots for eventual metabolic and/or synthetic use in many cell types, such a muscle, liver, and fat. In pancreatic islets, overt LD accumulation was detected in humans but not mice. LD buildup in islets was principally observed after roughly 11 years of age, increasing throughout adulthood under physiologic conditions, and also enriched in type 2 diabetes. To obtain insight into the role of LDs in human islet β-cell function, the levels of a key LD scaffold protein, perilipin 2 (PLIN2), were manipulated by lentiviral-mediated knockdown (KD) or overexpression (OE) in EndoCβH2-Cre cells, a human cell line with adult islet β-like properties. Glucose-stimulated insulin secretion was blunted in PLIN2KD cells and improved in PLIN2OE cells. An unbiased transcriptomic analysis revealed that limiting LD formation induced effectors of endoplasmic reticulum (ER) stress that compromised the expression of critical β-cell function and identity genes. These changes were essentially reversed by PLIN2OE or using the ER stress inhibitor, tauroursodeoxycholic acid. These results strongly suggest that LDs are essential for adult human islet β-cell activity by preserving FFA homeostasis.
Identifiants
pubmed: 34433630
pii: db21-0261
doi: 10.2337/db21-0261
pmc: PMC8564404
doi:
Substances chimiques
Lipids
0
PLIN2 protein, human
0
Perilipin-2
0
RNA, Messenger
0
Glucose
IY9XDZ35W2
Calcium
SY7Q814VUP
Banques de données
figshare
['10.2337/figshare.15747093']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2595-2607Subventions
Organisme : NIDDK NIH HHS
ID : R56 DK050203
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK090570
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020593
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK050203
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK126482
Pays : United States
Informations de copyright
© 2021 by the American Diabetes Association.
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