PMID- 30134843
OWN - NLM
STAT- MEDLINE
DCOM- 20181105
LR  - 20181114
IS  - 1471-2164 (Electronic)
IS  - 1471-2164 (Linking)
VI  - 19
IP  - 1
DP  - 2018 Aug 22
TI  - Identification of early biological changes in palmitate-treated isolated human 
      islets.
PG  - 629
LID - 10.1186/s12864-018-5008-z [doi]
LID - 629
AB  - BACKGROUND: Long-term exposure to elevated levels of free fatty acids (FFAs) is 
      deleterious for beta-cell function and may contribute to development of type 2 
      diabetes mellitus (T2DM). Whereas mechanisms of impaired glucose-stimulated 
      insulin secretion (GSIS) in FFA-treated beta-cells have been intensively studied, 
      biological events preceding the secretory failure, when GSIS is accentuated, are 
      poorly investigated. To identify these early events, we performed genome-wide 
      analysis of gene expression in isolated human islets exposed to fatty acid 
      palmitate for different time periods. RESULTS: Palmitate-treated human islets 
      showed decline in beta-cell function starting from day two. Affymetrix Human 
      Transcriptome Array 2.0 identified 903 differentially expressed genes (DEGs). 
      Mapping of the genes onto pathways using KEGG pathway enrichment analysis 
      predicted four islet biology-related pathways enriched prior but not after the 
      decline of islet function and three pathways enriched both prior and after the 
      decline of islet function. DEGs from these pathways were analyzed at the 
      transcript level. The results propose that in palmitate-treated human islets, at 
      early time points, protective events, including up-regulation of 
      metallothioneins, tRNA synthetases and fatty acid-metabolising proteins, dominate 
      over deleterious events, including inhibition of fatty acid detoxification 
      enzymes, which contributes to the enhanced GSIS. After prolonged exposure of 
      islets to palmitate, the protective events are outweighed by the deleterious 
      events, which leads to impaired GSIS. CONCLUSIONS: The study identifies temporal 
      order between different cellular events, which either promote or protect from 
      beta-cell failure. The sequence of these events should be considered when 
      developing strategies for prevention and treatment of the disease.
FAU - Sargsyan, Ernest
AU  - Sargsyan E
AUID- ORCID: 0000-0001-7519-6480
AD  - Department of Medical Cell Biology, Uppsala University, Box 571, 75123, Uppsala, 
      Sweden. ernest.sargsyan@mcb.uu.se.
AD  - Molecular Neuroscience Group, Institute of Molecular Biology, National Academy of 
      Sciences, 0014, Yerevan, Armenia. ernest.sargsyan@mcb.uu.se.
FAU - Cen, Jing
AU  - Cen J
AD  - Department of Medical Cell Biology, Uppsala University, Box 571, 75123, Uppsala, 
      Sweden.
FAU - Roomp, Kirsten
AU  - Roomp K
AD  - Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus 
      Belval, 7 avenue des Hauts fourneaux, 4362 Esch-Belval, Luxembourg City, 
      Luxembourg.
FAU - Schneider, Reinhard
AU  - Schneider R
AD  - Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus 
      Belval, 7 avenue des Hauts fourneaux, 4362 Esch-Belval, Luxembourg City, 
      Luxembourg.
FAU - Bergsten, Peter
AU  - Bergsten P
AD  - Department of Medical Cell Biology, Uppsala University, Box 571, 75123, Uppsala, 
      Sweden.
LA  - eng
GR  - 279 153/European Commission FP7/
PT  - Journal Article
DEP - 20180822
PL  - England
TA  - BMC Genomics
JT  - BMC genomics
JID - 100965258
RN  - 0 (Insulin)
RN  - 2V16EO95H1 (Palmitic Acid)
SB  - IM
MH  - Adult
MH  - Cells, Cultured
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Insulin/metabolism
MH  - Insulin-Secreting Cells/drug effects/physiology
MH  - Islets of Langerhans/*drug effects/physiology
MH  - Male
MH  - Microarray Analysis
MH  - Middle Aged
MH  - Palmitic Acid/*pharmacology
MH  - Primary Cell Culture
MH  - Time Factors
MH  - Transcriptome/drug effects
PMC - PMC6106933
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Ethical permission to use human 
      islets has been obtained from the Regional Ethical Review Board in Uppsala, 
      Sweden (EPN number 2010/006; 2010-02-10). CONSENT FOR PUBLICATION: Not 
      applicable. COMPETING INTERESTS: The authors declare that they have no competing 
      interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to 
      jurisdictional claims in published maps and institutional affiliations.
EDAT- 2018/08/24 06:00
MHDA- 2018/11/06 06:00
PMCR- 2018/08/22
CRDT- 2018/08/24 06:00
PHST- 2018/03/17 00:00 [received]
PHST- 2018/08/14 00:00 [accepted]
PHST- 2018/08/24 06:00 [entrez]
PHST- 2018/08/24 06:00 [pubmed]
PHST- 2018/11/06 06:00 [medline]
PHST- 2018/08/22 00:00 [pmc-release]
AID - 10.1186/s12864-018-5008-z [pii]
AID - 5008 [pii]
AID - 10.1186/s12864-018-5008-z [doi]
PST - epublish
SO  - BMC Genomics. 2018 Aug 22;19(1):629. doi: 10.1186/s12864-018-5008-z.