Background: Epidemiological studies show an association between air pollution and increased diabetes risk. However, the causal mechanism remains poorly understood. While it is believed that air pollution particles inhaled into the lungs cause diabetes via local and systemic inflammation, these particles also reach the gastrointestinal (GI) tract by swallowing and mucociliary clearance and could thereby initiate diabetes.

Research Design and Method:To differentiate between the effects of air pollution particles reaching the lungs vs. the GI tract, male C57B6/N mice were exposed to diesel exhaust particles (DEP; weekly dose 60µg) either by oral gavage (5 days/week) or intratracheal instillation (twice/week) for up to 6 months and glycemia monitored by glucose tolerance tests.

Results: Mice orally treated with DEP showed impaired glucose tolerance with reduced insulin secretion already after two months of treatment, while insulin sensitivity was not affected. Furthermore, orally treated mice showed a distorted balance of pro- and anti-inflammatory intestinal macrophages with a specific loss of the anti-inflammatory subpopulation, which normally constitutes the majority of intestinal macrophages in the healthy gut. Although mice receiving DEP by intratracheal instillation had increased monocyte recruitment to the lungs, they did not show any impairment in glucose tolerance up to 5 months.

Conclusion:Exposure of DEP to the GI tract but not the lungs causes impaired glucose tolerance and a concomitant decrease in anti-inflammatory intestinal macrophages. Our results provide new insights into the mechanism of air pollution-induced diabetes with the gut as the primary organ mediating the disease and thus could be targeted by potential prevention and therapeutic strategies.


A.J.T. Bosch: None. T.V. Rohm: None. S. AlAsfoor: None. T. Dervos: None. C. Cavelti-Weder: None.

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