Prenatal exposure to diesel exhaust PM 2.5 causes offspring β cell dysfunction in adulthood.

Environmental stressors that encounter in early-life and cause abnormal fetal and/or neonatal development may increase susceptibility to non-communicable diseases such as diabetes. Maternal exposure to ambient fine particulate matter (PM2.5) is associated with various fetal abnormalities, suggesting that it may program offspring's susceptibility to diabetes. In the present study, we therefore examined whether maternal exposure to diesel exhaust PM2.5 (DEP), one of the major sources of ambient PM2.5 in urban areas, programs adult offspring's glucose metabolism. Female C57BI/6J mice were intratracheally instilled with DEP or vehicle throughout a 7-wk preconceptional period, gestation, and lactation, and the glucose homeostasis of their adult male offspring was assessed. Intraperitoneal glucose tolerance test (IPGTT) revealed that the maternal exposure to DEP significantly impaired adult male offspring's glucose tolerance. Unexpectedly, it did not influence their insulin sensitivity, whereas it significantly decreased their glucose-induced insulin secretion (GIIS). This deficit in insulin secretion was corroborated by their significant decrease in arginine-induced insulin secretion. Histological analysis demonstrated that the deficit in insulin secretion was accompanied by the decrease in pancreatic islet and beta cell sizes. To differentiate the effects of maternal exposure to DEP before birth and during lactation, some offspring were cross-fostered once born. We did not observe any significant effect of cross-fostering on the glucose homeostasis of adult male offspring and the function and morphology of their beta cells. Prenatal exposure to DEP programs the morphology and function of beta cells and thus homeostatic regulation of glucose metabolism in adult male offspring.