PMID- 34232631
OWN - NLM
STAT- MEDLINE
DCOM- 20210809
LR  - 20210809
IS  - 1520-6882 (Electronic)
IS  - 0003-2700 (Linking)
VI  - 93
IP  - 28
DP  - 2021 Jul 20
TI  - Association of PM(2.5) with Insulin Resistance Signaling Pathways on a 
      Microfluidic Liver-Kidney Microphysiological System (LK-MPS) Device.
PG  - 9835-9844
LID - 10.1021/acs.analchem.1c01384 [doi]
AB  - Insulin resistance (IR) is a typical sign of metabolic dysregulation caused by 
      fine particulate matter (PM(2.5)), but the underlying signaling has not been 
      clearly determined. Herein, a microfluidic liver-kidney microphysiological system 
      (LK-MPS) is presented to assess the signaling pathways of IR generated by PM(2.5) 
      at 200 mug/mL for 24 h. The LK-MPS device consisted of a biomimetic liver-kidney 
      architecture and reconstructed two circulation paths: the liver metabolism-kidney 
      excretion (LM-KE) and kidney excretion-liver metabolism (KE-LM), by which PM(2.5) 
      is feasibly distributed in the two organs. Transmission electron microscopy (TEM) 
      analysis revealed that PM(2.5) can embed in the cytoplasm and nuclei, undergo 
      transport by vesicles, and lead to the destruction of mitochondria. Further 
      comprehensive immunofluorescence, enzyme-linked immunosorbent assays (ELISAs) and 
      untargeted metabolomic analyses confirmed that PM(2.5) disturbed the classic 
      IRS-1/AKT signaling pathway (INSR, IRS-1, PI3K, AKT, GLUT2, GLUT4, and FOXO1 
      downregulated) and IR-related metabolic pathways: UDP-hexosamine (UDP-GlcNAc), 
      gluconeogenesis (beta-d-glucose 6-phosphate), and lipid biosynthesis (ceramide (Cer) 
      and triacylglycerol (TG)) pathways, leading to the disorder of glucose levels. 
      Collectively, these disorders aggravate hepatic and renal IR. Pearson's 
      correlation coefficient test showed that elemental carbon (EC), polycyclic 
      aromatic hydrocarbons (PAHs), and metals (Ca, Co, and V) were negatively 
      correlated to the dysregulated proteins (INSR, IRS-1, AKT, FOXO1, GLUT2, and 
      GLUT4). These findings may partially explain IR-related signaling pathways 
      triggered by PM(2.5).
FAU - Duan, Xiaoxiao
AU  - Duan X
AD  - Shanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), 
      Department of Environmental Science & Engineering, Fudan University, 2005 Songhu 
      Road, Shanghai 200438, P. R. China.
FAU - Zhang, Xinlian
AU  - Zhang X
AD  - Shanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), 
      Department of Environmental Science & Engineering, Fudan University, 2005 Songhu 
      Road, Shanghai 200438, P. R. China.
FAU - Chen, Jianmin
AU  - Chen J
AUID- ORCID: 0000-0001-5859-3070
AD  - Shanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), 
      Department of Environmental Science & Engineering, Fudan University, 2005 Songhu 
      Road, Shanghai 200438, P. R. China.
FAU - Xiao, Mingming
AU  - Xiao M
AD  - Shanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), 
      Department of Environmental Science & Engineering, Fudan University, 2005 Songhu 
      Road, Shanghai 200438, P. R. China.
FAU - Zhao, Wang
AU  - Zhao W
AD  - Shanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), 
      Department of Environmental Science & Engineering, Fudan University, 2005 Songhu 
      Road, Shanghai 200438, P. R. China.
FAU - Liu, Sixiu
AU  - Liu S
AUID- ORCID: 0000-0001-7094-5892
AD  - Shanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), 
      Department of Environmental Science & Engineering, Fudan University, 2005 Songhu 
      Road, Shanghai 200438, P. R. China.
FAU - Sui, Guodong
AU  - Sui G
AUID- ORCID: 0000-0002-6751-0852
AD  - Shanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), 
      Department of Environmental Science & Engineering, Fudan University, 2005 Songhu 
      Road, Shanghai 200438, P. R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210707
PL  - United States
TA  - Anal Chem
JT  - Analytical chemistry
JID - 0370536
RN  - 0 (Insulin)
RN  - 0 (Particulate Matter)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Humans
MH  - *Insulin
MH  - *Insulin Resistance
MH  - Kidney/metabolism
MH  - Liver/metabolism
MH  - Microfluidics
MH  - Particulate Matter/toxicity
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
EDAT- 2021/07/08 06:00
MHDA- 2021/08/10 06:00
CRDT- 2021/07/07 17:10
PHST- 2021/07/08 06:00 [pubmed]
PHST- 2021/08/10 06:00 [medline]
PHST- 2021/07/07 17:10 [entrez]
AID - 10.1021/acs.analchem.1c01384 [doi]
PST - ppublish
SO  - Anal Chem. 2021 Jul 20;93(28):9835-9844. doi: 10.1021/acs.analchem.1c01384. Epub 
      2021 Jul 7.