PMID- 29589392
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 2093-596X (Print)
IS  - 2093-5978 (Electronic)
IS  - 2093-596X (Linking)
VI  - 33
IP  - 1
DP  - 2018 Mar
TI  - Pioglitazone Attenuates Palmitate-Induced Inflammation and Endoplasmic Reticulum 
      Stress in Pancreatic beta-Cells.
PG  - 105-113
LID - 10.3803/EnM.2018.33.1.105 [doi]
AB  - BACKGROUND: The nuclear receptor peroxisome proliferator-activator gamma (PPARgamma) 
      is a useful therapeutic target for obesity and diabetes, but its role in 
      protecting beta-cell function and viability is unclear. METHODS: To identify the 
      potential functions of PPARgamma in beta-cells, we treated mouse insulinoma 6 (MIN6) 
      cells with the PPARgamma agonist pioglitazone in conditions of lipotoxicity, 
      endoplasmic reticulum (ER) stress, and inflammation. RESULTS: Palmitate-treated 
      cells incubated with pioglitazone exhibited significant improvements in 
      glucose-stimulated insulin secretion and the repression of apoptosis, as shown by 
      decreased caspase-3 cleavage and poly (adenosine diphosphate [ADP]-ribose) 
      polymerase activity. Pioglitazone also reversed the palmitate-induced expression 
      of inflammatory cytokines (tumor necrosis factor alpha, interleukin 6 [IL-6], and 
      IL-1beta) and ER stress markers (phosphor-eukaryotic translation initiation factor 
      2alpha, glucose-regulated protein 78 [GRP78], cleaved-activating transcription factor 
      6 [ATF6], and C/EBP homologous protein [CHOP]), and pioglitazone significantly 
      attenuated inflammation and ER stress in lipopolysaccharide- or 
      tunicamycin-treated MIN6 cells. The protective effect of pioglitazone was also 
      tested in pancreatic islets from high-fat-fed KK-Ay mice administered 0.02% 
      (wt/wt) pioglitazone or vehicle for 6 weeks. Pioglitazone remarkably reduced the 
      expression of ATF6alpha, GRP78, and monocyte chemoattractant protein-1, prevented 
      alpha-cell infiltration into the pancreatic islets, and upregulated glucose 
      transporter 2 (Glut2) expression in beta-cells. Moreover, the preservation of 
      beta-cells by pioglitazone was accompanied by a significant reduction of blood 
      glucose levels. CONCLUSION: Altogether, these results support the proposal that 
      PPARgamma agonists not only suppress insulin resistance, but also prevent beta-cell 
      impairment via protection against ER stress and inflammation. The activation of 
      PPARgamma might be a new therapeutic approach for improving beta-cell survival and 
      insulin secretion in patients with diabetes mellitus.
CI  - Copyright (c) 2018 Korean Endocrine Society.
FAU - Hong, Seok Woo
AU  - Hong SW
AUID- ORCID: 0000-0002-3288-1901
AD  - Institute of Medical Research, Kangbuk Samsung Hospital, Sungkyunkwan University 
      School of Medicine, Seoul, Korea.
FAU - Lee, Jinmi
AU  - Lee J
AD  - Institute of Medical Research, Kangbuk Samsung Hospital, Sungkyunkwan University 
      School of Medicine, Seoul, Korea.
FAU - Cho, Jung Hwan
AU  - Cho JH
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Kwon, Hyemi
AU  - Kwon H
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Park, Se Eun
AU  - Park SE
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Rhee, Eun Jung
AU  - Rhee EJ
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Park, Cheol Young
AU  - Park CY
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Oh, Ki Won
AU  - Oh KW
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Park, Sung Woo
AU  - Park SW
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Lee, Won Young
AU  - Lee WY
AUID- ORCID: 0000-0002-1082-7592
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea. drlwy@hanmail.net.
LA  - eng
PT  - Journal Article
PL  - Korea (South)
TA  - Endocrinol Metab (Seoul)
JT  - Endocrinology and metabolism (Seoul, Korea)
JID - 101554139
PMC - PMC5874186
OTO - NOTNLM
OT  - Endoplasmic reticulum stress
OT  - Glucolipotoxicity
OT  - Inflammation
OT  - Insulin-secreting cells
OT  - Pioglitazone
COIS- No potential conflict of interest relevant to this article was reported.
EDAT- 2018/03/29 06:00
MHDA- 2018/03/29 06:01
PMCR- 2018/03/01
CRDT- 2018/03/29 06:00
PHST- 2017/12/05 00:00 [received]
PHST- 2018/01/08 00:00 [revised]
PHST- 2018/01/09 00:00 [accepted]
PHST- 2018/03/29 06:00 [entrez]
PHST- 2018/03/29 06:00 [pubmed]
PHST- 2018/03/29 06:01 [medline]
PHST- 2018/03/01 00:00 [pmc-release]
AID - 33.105 [pii]
AID - 10.3803/EnM.2018.33.1.105 [doi]
PST - ppublish
SO  - Endocrinol Metab (Seoul). 2018 Mar;33(1):105-113. doi: 10.3803/EnM.2018.33.1.105.