PMID- 28465244
OWN - NLM
STAT- MEDLINE
DCOM- 20170911
LR  - 20170911
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 181
DP  - 2017 Jul 15
TI  - PERK/eIF2alpha contributes to changes of insulin signaling in HepG2 cell induced by 
      intermittent hypoxia.
PG  - 17-22
LID - S0024-3205(17)30201-1 [pii]
LID - 10.1016/j.lfs.2017.04.022 [doi]
AB  - AIMS: Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with 
      abnormal glucose metabolism. Nowadays, endoplasmic reticulum (ER) stress emerges 
      as an important mechanism underlying the development of type 2 diabetes mellitus 
      (T2DM). However, it remains unclear that intermittent hypoxia (IH) could induce 
      ER stress, resulting in abnormality of glucose metabolism. Thus, in the current 
      study we explore the changes of insulin signaling under IH and the role of ER 
      stress underlying these changes. MAIN METHODS: HepG2 cells were exposed to room 
      air (RA) or IH for 8h, 16h and 24h respectively. Oxygen concentration in IH 
      groups was in a dynamic cycle from 21% to 1% every 5min, while it remained at 21% 
      in RA groups. Insulin was added into cell culture medium for AKT and p-AKT 
      measurement. In another experiment set, HepG2 cells were pre-cultured with 4-PBA 
      prior to IH or RA exposure. Expression of AKT, p-AKT, p-JNK, p-IRE1, p-PERK and 
      p-eIF2alpha was examined by Western Blot. KEY FINDINGS: Compared with RA, p-AKT 
      expression in HepG2 cells under IH for 24h was significantly lower even with 
      insulin treatment. Expression of p-JNK, p-IRE1, ATF6, p-PERK and p-eIF2alpha were 
      upregulated. p-AKT level in HepG2 with 4-PBA preculture under IH was restored. 
      p-PERK and p-eIF2alpha expression in HepG2 cells in IH groups with 4-PBA preculture 
      were inhibited while levels of p-JNK and p-IRE1 remained unchanged. SIGNIFICANCE: 
      IH, the hallmarker of OSAHS, could disturb insulin signaling via activating 
      PERK/eIF2alpha.
CI  - Copyright (c) 2017. Published by Elsevier Inc.
FAU - Yi, Huahua
AU  - Yi H
AD  - Department of Respiratory Medicine, Ruijin Hospital, No. 197, Ruijin Er Road., 
      Shanghai, 200025, China.
FAU - Gu, Chenjuan
AU  - Gu C
AD  - Department of Respiratory Medicine, Ruijin Hospital, No. 197, Ruijin Er Road., 
      Shanghai, 200025, China.
FAU - Li, Min
AU  - Li M
AD  - Department of Respiratory Medicine, Ruijin Hospital, No. 197, Ruijin Er Road., 
      Shanghai, 200025, China. Electronic address: limin_4212@163.com.
FAU - Zhang, Zhiguo
AU  - Zhang Z
AD  - Department of Endocrine and Metabolism Institute, Ruijin Hospital, No. 197, 
      Ruijin Er Road, Shanghai 200025, China.
FAU - Li, Qingyun
AU  - Li Q
AD  - Department of Respiratory Medicine, Ruijin Hospital, No. 197, Ruijin Er Road., 
      Shanghai, 200025, China.
FAU - Feng, Jing
AU  - Feng J
AD  - Department of Respiratory Medicine, Ruijin Hospital, No. 197, Ruijin Er Road., 
      Shanghai, 200025, China.
FAU - Zhou, Jun
AU  - Zhou J
AD  - Department of Respiratory Medicine, Ruijin Hospital, No. 197, Ruijin Er Road., 
      Shanghai, 200025, China.
FAU - Du, Juan
AU  - Du J
AD  - Department of Respiratory Medicine, Ruijin Hospital, No. 197, Ruijin Er Road., 
      Shanghai, 200025, China.
LA  - eng
PT  - Journal Article
DEP - 20170429
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (4-phenylbutylamine)
RN  - 0 (Butylamines)
RN  - 0 (Insulin)
RN  - EC 2.7.11.1 (PERK kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Blotting, Western
MH  - Butylamines/pharmacology
MH  - Endoplasmic Reticulum Stress/*physiology
MH  - Gene Expression Regulation/genetics
MH  - Glucose/metabolism
MH  - Hep G2 Cells
MH  - Humans
MH  - Hypoxia/*complications
MH  - Insulin/administration & dosage/*metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/physiology
MH  - Sleep Apnea, Obstructive/*physiopathology
MH  - Time Factors
MH  - Up-Regulation/genetics
MH  - eIF-2 Kinase/*metabolism
OTO - NOTNLM
OT  - AKT
OT  - ER stress
OT  - Intermittent hypoxia
OT  - PERK
OT  - eIF2alpha
EDAT- 2017/05/04 06:00
MHDA- 2017/09/12 06:00
CRDT- 2017/05/04 06:00
PHST- 2017/01/15 00:00 [received]
PHST- 2017/04/19 00:00 [revised]
PHST- 2017/04/28 00:00 [accepted]
PHST- 2017/05/04 06:00 [pubmed]
PHST- 2017/09/12 06:00 [medline]
PHST- 2017/05/04 06:00 [entrez]
AID - S0024-3205(17)30201-1 [pii]
AID - 10.1016/j.lfs.2017.04.022 [doi]
PST - ppublish
SO  - Life Sci. 2017 Jul 15;181:17-22. doi: 10.1016/j.lfs.2017.04.022. Epub 2017 Apr 
      29.