Type 2 diabetes mellitus (T2DM) is one of the leading causes of death around the world. Epidemiological studies have uncovered that in addition to lack of exercise and over-nutrition, factors in the physical environment such as pollutants may also be associated with T2DM. We and others have provided evidence that airborne particulate matter <2.5 ?m (PM2.5) exposure modulates key processes in the pathogenesis of T2DM including insulin resistance, visceral fat accumulation, pro-inflammatory immune activation, and hepatic endoplasmic reticulum stress. Integrated pathways by which exposure may modulate these diverse effects are currently lacking. In this proposal, we postulate that PM2.5 exposure induces hypothalamic Inhibitor ?B Kinase 2 (IKK2)/Nuclear Factor-?B (NF-?B) activation with consequent changes in peripheral insulin sensitivity/inflammation, and thus propose to pursue 3 discrete yet linked aims using state of art in vivo exposures that mimic real-world exposure to air pollution.
Aim 1 : To determine if PM2.5 exposure induces hypothalamic IKK2/NF-?B activation and inflammatory response.
Aim 2 : To determine if central IKK2/NF-?B signaling is essential for PM2.5 exposure-induced abnormalities in insulin sensitivity/inflammation.
Aim 3. To determine if TNF? is essential for PM2.5 exposure-induced hypothalamic inflammation and insulin resistance. Our results will provide a renewed understanding of the protean effects of air pollution exposure and have obvious global public health implications.

Public Health Relevance

Airborne particles, the main ingredient of haze, smoke, and airborne dust, present serious air quality problems in many areas of the United States, and can occur year-round and cause a number of serious health problems, even at concentrations found in many major cities. This project investigates the role of central nervous system in airborne particle exposure-induced diabetes. The results will not only provide insight into the mechanism whereby airborne particle exposure leads to diabetes but also facilitate the development of new models and preventions for this serious public health risk.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-DKUS-C (90))
Program Officer
Heindel, Jerrold
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Maryland Baltimore
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Ying, Zhekang; Allen, Katryn; Zhong, Jixin et al. (2016) Subacute inhalation exposure to ozone induces systemic inflammation but not insulin resistance in a diabetic mouse model. Inhal Toxicol 28:155-63
Ying, Zhekang; Chen, Minjie; Xie, Xiaoyun et al. (2016) Lipoicmethylenedioxyphenol Reduces Experimental Atherosclerosis through Activation of Nrf2 Signaling. PLoS One 11:e0148305
Ying, Zhekang; Xie, Xiaoyun; Bai, Yuntao et al. (2015) Exposure to concentrated ambient particulate matter induces reversible increase of heart weight in spontaneously hypertensive rats. Part Fibre Toxicol 12:15
Ying, Zhekang; Xie, Xiaoyun; Chen, Minjie et al. (2015) Alpha-lipoic acid activates eNOS through activation of PI3-kinase/Akt signaling pathway. Vascul Pharmacol 64:28-35
Chen, Minjie; Ma, Lan; Hall, John E et al. (2015) Dual regulation of tumor necrosis factor-α on myosin light chain phosphorylation in vascular smooth muscle. Am J Physiol Heart Circ Physiol 308:H398-406