Abstract
To elucidate the mechanism of how the liver participates in PM2.5-caused insulin resistance. A novel Wistar rat model was developed in this study by instilling a suspension of lyophilized PM2.5 sample (2.5 mg/kg, 5 mg/kg, or 10 mg/kg) collected from the atmosphere. Systemic insulin resistance indicators, including serum fasting blood glucose (FBG), fasting insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and hemoglobin A1 (HbA1), were upregulated by the PM2.5 instillation. The area under the curve (AUCglu) calculated by intraperitoneal glucose tolerance testing (IPGTT) was also significantly greater in the PM2.5 instillation groups. Additionally, PM2.5 instillation was found to cause liver damage and inflammation. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly elevated by PM2.5 instillation. PM2.5 also triggered IL-6 and TNF-α transcription but inhibited mRNA synthesis and suppressed signaling activation of the insulin-phosphoinositide 3-kinase- (PI3K-) Akt-glucose transporter 2 (GLUT2) pathway in the rat liver by reducing the ratio of phosphorylated Akt to phosphorylated insulin receptor substrate 1 (IRS-1). Thus, PM2.5-induced inflammation activation and insulin signaling inhibition in the rat liver contribute to the development of systemic insulin resistance.
Highlights
According to the World Health Organization, the global prevalence of diabetes in adults over 18 years old increased from 4.7% in 1980 to 8.5% in 2014, while the prevalence of diabetes in China had already reached 9.7% in 2010 [1]
The liver is one of the most important organs involved in insulin resistance, and some studies have shown that PM2.5 exposure induces liver damage [8, 9]; another study has found no significant effect of PM2.5 on the liver [10]
To study the effect of PM2.5 instillation on systemic insulin resistance in rats, the levels of fasting blood glucose (FBG), fasting insulin (FINS), HbA1c, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were examined in all five groups (Figures 1(a)– 1(d) and Table 2(a))
Summary
According to the World Health Organization, the global prevalence of diabetes in adults over 18 years old increased from 4.7% in 1980 to 8.5% in 2014, while the prevalence of diabetes in China had already reached 9.7% in 2010 [1]. Large numbers of related studies have shown that the main mechanism involved in the development and progression of type 2 diabetes is insulin resistance, which implies a significant reduction in the physiological effects of uptake and utilization of glucose [2]. The liver is one of the most important organs involved in insulin resistance, and some studies have shown that PM2.5 exposure induces liver damage [8, 9]; another study has found no significant effect of PM2.5 on the liver [10]. To systematically analyze the hepatic mechanism involved in the development of systemic insulin resistance, we performed PM2.5 instillation (0, 0.75, 2.5, 5, or 10 mg/kg) in Wistar rats for 8 weeks. The PM2.5-induced phosphorylation of Akt and insulin receptor substrate 1 (IRS-1) in the rat liver was evaluated and compared by western blotting
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