PMID- 34433630
OWN - NLM
STAT- MEDLINE
DCOM- 20211229
LR  - 20211229
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 70
IP  - 11
DP  - 2021 Nov
TI  - Lipid Droplets Protect Human beta-Cells From Lipotoxicity-Induced Stress and Cell 
      Identity Changes.
PG  - 2595-2607
LID - 10.2337/db21-0261 [doi]
AB  - 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 beta-cell function, the levels of a key LD scaffold protein, perilipin 2 
      (PLIN2), were manipulated by lentiviral-mediated knockdown (KD) or overexpression 
      (OE) in EndoCbetaH2-Cre cells, a human cell line with adult islet beta-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 beta-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 beta-cell activity by preserving FFA homeostasis.
CI  - (c) 2021 by the American Diabetes Association.
FAU - Tong, Xin
AU  - Tong X
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University, 
      Nashville, TN.
FAU - Stein, Roland
AU  - Stein R
AUID- ORCID: 0000-0001-9192-8661
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University, 
      Nashville, TN roland.stein@vanderbilt.edu.
LA  - eng
SI  - figshare/10.2337/figshare.15747093
GR  - R56 DK050203/DK/NIDDK NIH HHS/United States
GR  - R01 DK090570/DK/NIDDK NIH HHS/United States
GR  - P30 DK020593/DK/NIDDK NIH HHS/United States
GR  - R01 DK050203/DK/NIDDK NIH HHS/United States
GR  - R01 DK126482/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210825
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Lipids)
RN  - 0 (PLIN2 protein, human)
RN  - 0 (Perilipin-2)
RN  - 0 (RNA, Messenger)
RN  - IY9XDZ35W2 (Glucose)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium
MH  - Cell Differentiation
MH  - Cell Line
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Glucose/pharmacology
MH  - Homeostasis
MH  - Humans
MH  - Insulin Secretion/drug effects
MH  - Insulin-Secreting Cells/*metabolism
MH  - Lipid Droplets/*metabolism
MH  - Lipid Metabolism
MH  - Lipids/*toxicity
MH  - Perilipin-2/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Stress, Physiological
PMC - PMC8564404
EDAT- 2021/08/27 06:00
MHDA- 2021/12/30 06:00
PMCR- 2021/08/25
CRDT- 2021/08/26 05:36
PHST- 2021/03/26 00:00 [received]
PHST- 2021/08/19 00:00 [accepted]
PHST- 2021/08/27 06:00 [pubmed]
PHST- 2021/12/30 06:00 [medline]
PHST- 2021/08/26 05:36 [entrez]
PHST- 2021/08/25 00:00 [pmc-release]
AID - db21-0261 [pii]
AID - 210261 [pii]
AID - 10.2337/db21-0261 [doi]
PST - ppublish
SO  - Diabetes. 2021 Nov;70(11):2595-2607. doi: 10.2337/db21-0261. Epub 2021 Aug 25.