2322-PUB: PM2.5 Accelerated Impaired Pancreatic a-Cells by Increasing Expression of Inflammatory Factors in Mice with Streptozotocin

Abstract

We investigated how PM2.5 exposure could affect glucose homeostasis in mice with streptozotocin (STZ). Male C57BL/6 mice were housed under filtered air (FA) or PM2.5 for 12 weeks and then received intraperitoneal injection of STZ (40 mg/kg of bodyweight) or acetic buffer daily for consecutive five days. Four weeks after the last injection, fasting glucose test was performed. Cholesterol and triglyceride levels were determined in the plasma and liver. Homeostasis Model Assessment of β cell function (Homa-β) were computed using fasting insulin and glucose. Interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels in plasma, visceral adipose tissues, macrophage RAW264.7 and pancreatic β-cells MIN6 treated with PM2.5 (0-50 μg/ml) were quantified by ELISA. Before STZ injection, fasting blood glucose (FBG) levels were similar between FA and PM2.5 groups (p=0.92). After STZ injection, FBG levels were 1.2- fold higher in mice pre-exposed to PM2.5 than those pre-exposed to FA (p=0.17). When taking FBG levels ≥7 mmol/L as the criteria for impaired glucose tolerance, its incidence was 53.3% and 77.8% in FA and PM2.5 groups, respectively (p=0.08). IL-1β and TNF-α levels in the adipose tissues were greater in diabetic mice pre-exposed to PM2.5 than diabetic mice pre-exposed to FA (p<0.05 for all). The addition of PM2.5 stimulated IL-1β and TNF-α production in macrophages and pancreatic β-cells, and impaired the incretion of insulin in MIN6 cells in a dose-dependent manner. In conclusion, pre-exposure of PM2.5 impaired pancreatic β-cells in mice upon STZ injection, partially via enhanced inflammation and suppressed the incretion of insulin. Disclosure R. Yin: None. L. Yang: None. J. Lang: None. D. Zhao: None. Funding National Natural Science Foundation of China (81800768)