Association between the expression of GLUT-2, GCK in hepatocytes and insulin resistance in rats treated by intermittent hypoxia

Abstract

Objective To determine the expression of glucose transporter-2 (GLUT-2) and glucokinase (GCK) in hepatocytes of intermittent hypoxic rat model, and explore the possible mechanisms of insulin resistance caused by intermittent hypoxia. Methods Twenty-four healthy male Sprague-Dawley (SD) rats at 6-week age were divided into control group (NC group), 4 weeks of intermittent hypoxia group (IH4 group) and 8 weeks of intermittent hypoxia group (IH8 group) according to the random number table, with 8 rats in each group. According to the preset ventilation mode, rats in intermittent groups were exposed in intermittent hypoxia for 8 hours every day, whereas rats in NC group were exposed in intermittent compressed air for the same time with IH4 group. Fasting blood glucose and fasting insulin were tested after experiment; homeostasis model assessment-insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI) were calculated. The expression of hepatic GLUT-2 and GCK protein were measured by immunohistochemical method, and were quantitatively analyzed by the average gray value. Results Compared with NC group, fasting blood glucose, fasting insulin and HOMA-IR were increased, whereas ISI were decreased in IH4 group and IH8 group, especially in IH8 group (F=161.92, 51.46, 126.99, 83.87, all P<0.05). Compared with NC group, the expression of GLUT-2 and GCK in hepatic cells were decreased in IH4 group and IH8 group, especially in IH8 group (F=184.91, 240.85, all P<0.05). Pearson correlation analysis showed that the level of GLUT-2 and GCK were negatively correlated with ISI(r=-0.886, -0.906, all P<0.05), and positively correlated with HOMA-IR(r=0.894, 0.869, all P<0.05). Conclusion Intermittent hypoxia decreases the expression of GLUT-2 and GCK, which may participate in the occurrence of insulin resistance under the condition of intermittent hypoxia. Key words: Intermittent hypoxia; Insulin resistance; Glucose transporter-2; Glucokinase