Objective  To investigate the effect of subchronic arsenic exposure on hepatic glucose metabolism and its molecular mechanism in rats.

  Methods  Totally 40 Sprague-Dawley (SD) rats were randomly divided into a control group (with intragastric administration of distilled water) and three groups with intragastric administration of sodium arsenite (NaAsO₂) at doses of 2, 4, 8 mg/kg once a week continuously for 12 weeks. The body weight of the rats was recorded weekly. By the end of the administrations, oral glucose tolerance test (OGTT) was performed and samples of hair and liver were collected for all the rats. The content of arsenic in hair, the content of glycogen in liver and the activities of hexokinase (HK) and pyruvate kinase (PK) were detected. Ppathological changes of liver were observed. The expressions of phosphoinosistide 3-kinase (PI3K), protein kinase B (AKT), glycogen synthase kinase-3 β (GSK3β), phosphorylated glycogen synthase kinase-3 β(P-GSK3β), glucose transporter 2 (GLUT2) and glucose transporter 4 (GLUT4) were determined with Western blot.

  Results  The body weight decreased at 8th and 12th week for the rats exposed to high and moderate NaAsO₂. Significantly higher hair arsenic content (mg/kg) was measured in the rats exposed to high/moderate/low NaAsO₂ compared with that of control rats (49.24 ± 8.02/21.06 ± 3.42/14.59 ± 2.00 vs. 0.43 ± 0.08; all P < 0.05). Abnormal glucose tolerance and decreased liver glycogen were also detected in the rats with NaAsO₂ exposure. In comparison to control rats, the rats treated with high/moderate NaAsO₂ had significantly decreased HK (1.94 ± 0.11/2.14 ± 0.03 vs. 2.84 ± 0.08) U/mg and PK (43.64 ± 1.05/44.26 ± 0.10 vs. 55.95 ± 0.96) U/mg (P < 0.05 for all). Pathological observation revealed mild hepatic steatosis and increased round vacuoles of hepatocytes in the rats with high and moderate NaAsO₂ treatment. Contrasted to the protein expressions of PI3K (1.03 ± 0.02), AKT (1.36 ± 0.02), P-GSK3β/GSK3β (0.96 ± 0.04), GLUT2 (1.24 ± 0.12), and GLUT4 (1.80 ± 0.15) in the control rats, following significantly decreased protein expressions were identified in the rats exposed to various doses of NaAsO₂: PI3K (0.76 ± 0.06), AKT (1.19 ± 0.04), P-GSK3β/GSK3β(0.76 ± 0.03), GLUT2 (0.82 ± 0.11), and GLUT4 (0.88 ± 0.14) in the rats treated with high dose; AKT (1.08 ± 0.10) and GLUT4 (1.38 ± 0.10) in the rats with moderate dose; and GLUT4 (1.10 ± 0.12) in the rats with low dose (all P < 0.05 ).

  Conclusion  Subchronic arsenic exposure can induce hepatic glucose metabolism disorder in rats; the effect may be related to changes in hepatic glycogen, activities of glucose metabolic enzymes, and expressions of relevant proteins.