PMID- 24142192
OWN - NLM
STAT- MEDLINE
DCOM- 20140527
LR  - 20131024
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 32
IP  - 6
DP  - 2013 Dec
TI  - Palmitate induces autophagy in pancreatic beta-cells via endoplasmic reticulum 
      stress and its downstream JNK pathway.
PG  - 1401-6
LID - 10.3892/ijmm.2013.1530 [doi]
AB  - Endoplasmic reticulum (ER) stress and autophagy have both been reported to be 
      associated with lipotoxicity in beta-cells, yet the relationship between them has 
      not been fully clarified. In the present study, we tested the hypothesis that the 
      ER stress-autophagic pathway in beta-cells is a downstream pathway activated 
      following saturated fatty acid treatment. Mouse insulinoma (MIN6) beta-cells were 
      treated with either palmitate or thapsigargin (TG) with or without various 
      inhibitors. The results indicated that palmitate strongly enhanced the protein 
      expression of microtubule-associated protein 1 light chain 3 (LC3)-II. 
      Furthermore, the expression levels of ER stress markers, BiP and CHOP, and 
      phosphorylation levels of JNK were increased after palmitate treatment. In 
      addition, palmitate-induced autophagy was blocked by 500 microM of the ER stress 
      inhibitor tauroursodeoxycholic acid (TUDCA) or 20 microM JNK inhibitor SP600125. In 
      turn, the phosphorylation of Akt (Ser473) was also downregulated by palmitate, 
      while the levels of insulin receptor beta (IRbeta) were not reduced. A further increase 
      in LC3-II levels was observed in cells treated with both palmitate and 50 microM 
      PI3K/Akt inhibitor LY294002 compared with cells treated with palmitate alone. 
      Palmitate-induced phospho-Akt (Ser473) downregulation was also inhibited by TUDCA 
      or SP600125. Pretreatment with the autophagy inhibitor 3-methyladenine (3-MA, 
      5 mM) for 1 h increased the expression of ER stress markers, and enhanced cell 
      injuries caused by 0.1 microM TG, including decreased cell viability and insulin 
      secretion. Palmitate induces autophagy in pancreatic beta-cells possibly through 
      activation of ER stress and its downstream JNK pathway. Palmitate-induced 
      autophagy may protect beta-cells against cell injuries caused by ER stress.
FAU - Chen, Ying-Ying
AU  - Chen YY
AD  - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, P.R. 
      China.
FAU - Sun, Lian-Qing
AU  - Sun LQ
FAU - Wang, Bao-An
AU  - Wang BA
FAU - Zou, Xiao-Man
AU  - Zou XM
FAU - Mu, Yi-Ming
AU  - Mu YM
FAU - Lu, Ju-Ming
AU  - Lu JM
LA  - eng
PT  - Journal Article
DEP - 20131018
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Palmitates)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Cell Line, Tumor
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Insulin-Secreting Cells/drug effects/*enzymology/*pathology
MH  - MAP Kinase Signaling System/*drug effects
MH  - Mice
MH  - Models, Biological
MH  - Palmitates/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Up-Regulation/drug effects
EDAT- 2013/10/22 06:00
MHDA- 2014/05/28 06:00
CRDT- 2013/10/22 06:00
PHST- 2012/12/01 00:00 [received]
PHST- 2013/02/11 00:00 [accepted]
PHST- 2013/10/22 06:00 [entrez]
PHST- 2013/10/22 06:00 [pubmed]
PHST- 2014/05/28 06:00 [medline]
AID - 10.3892/ijmm.2013.1530 [doi]
PST - ppublish
SO  - Int J Mol Med. 2013 Dec;32(6):1401-6. doi: 10.3892/ijmm.2013.1530. Epub 2013 Oct 
      18.