title: Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus.
abstract: BACKGROUND
  Prior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (<2.5 μm in aerodynamic diameter, PM2.5) and development of insulin resistance/Type II diabetes mellitus. This study was designed to investigate whether inhalational exposure of concentrated PM2.5 in a genetically susceptible animal model would result in abnormalities in energy metabolism and exacerbation of peripheral glycemic control.
  
  
  METHODS
  KKay mice, which are susceptible to Type II DM, were assigned to either concentrated ambient PM2.5 or filtered air (FA) for 5-8 weeks via a whole body exposure system. Glucose tolerance, insulin sensitivity, oxygen consumption and heat production were evaluated. At euthanasia, blood, spleen and visceral adipose tissue were collected to measure inflammatory cells using flow cytometry. Standard immnunohistochemical methods, western blotting and quantitative PCR were used to assess targets of interest.
  
  
  RESULTS
  PM2.5 exposure influenced energy metabolism including O2 consumption, CO2 production, respiratory exchange ratio and thermogenesis. These changes were accompanied by worsened insulin resistance, visceral adiposity and inflammation in spleen and visceral adipose depots. Plasma adiponectin were decreased in response to PM2.5 exposure while leptin levels increased. PM2.5 exposure resulted in a significant increase in expression of inflammatory genes and decreased UCP1 expression in brown adipose tissue and activated p38 and ERK pathways in the liver of the KKay mice.
  
  
  CONCLUSIONS
  Concentrated ambient PM2.5 exposure impairs energy metabolism, concomitant with abnormalities in glucose homeostasis, increased inflammation in insulin responsive organs, brown adipose inflammation and results in imbalance in circulating leptin/adiponectin levels in a genetically susceptible diabetic model. These results provide additional insights into the mechanisms surrounding air pollution mediated susceptibility to Type II DM.
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Liu
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Bai
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xu
authors.forename: Lixian
authors.initials: L
authors.lastname: Sun
authors.forename: Aixia
authors.initials: A
authors.lastname: Wang
authors.forename: Tse-Yao
authors.initials: TY
authors.lastname: Wang
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Maurya
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
authors.forename: Masako
authors.initials: M
authors.lastname: Morishita
authors.forename: Jack
authors.initials: J
authors.lastname: Harkema
authors.forename: Zhekang
authors.initials: Z
authors.lastname: Ying
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Division of Cardiovascular Medicine, University of Maryland, Baltimore, MD, USA. srajagopalan@medicine.umaryland.edu.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
mesh_terms: D052437:Adipocytes, Brown / Q000187:drug effects; D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D005434:Flow Cytometry; D006706:Homeostasis / Q000187:drug effects; D007328:Insulin / Q000502:physiology; D051379:Mice; D009213:Myography; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D022722:Thermogenesis / Q000187:drug effects
chemical_list: D000393:Air Pollutants; D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D052638:Particulate Matter