Abstract

To observe the expression of insulin receptor substrate-2 (IRS-2) mRNA and protein, and its tyrosine phosphorylation in hepatic tissue of chronic hepatitis B (CHB) patients, and to explore the role of IRS-2 on insulin resistance in CHB patients. Eighteen patients with CHB were included, and 6 individuals with normal liver function were enrolled as control. Based on the insulin resistance index determined by homeostasis model assessment (HOMA), CHB patients were further divided into CHB without insulin resistance group (<2.69, n=10) and CHB with insulin resistance group (>2.69, n=8). Hepatic tissues were harvested from all patients during operation or with liver biopsy. The mRNA expression of IRS-2 in liver tissue was assessed by reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression of IRS-2 was detected by Western blotting. Immunoprecipitation and enhanced chemiluminescent technique were used to measure the tyrosine phosphorylation of IRS-2. In CHB without insulin resistance group, the mRNA expression (0.38+/-0.06), the protein expression (0.94+/-0.18) and the tyrosine phosphorylation (0.78+/-0.09) of IRS-2 in hepatic tissue were decreased, but without statistically significant difference (all P>0.05), as compared to those in control group (0.45+/-0.11, 0.99+/-0.20, 1.00+/-0.23, respectively). In CHB with insulin resistance group, the mRNA expression (0.26+/-0.08), the protein expression (0.67+/-0.11) and the tyrosine phosphorylation (0.63+/-0.14) of IRS-2 in hepatic tissue were significantly decreased compared with those of the control group with statistically significant difference (P<0.05 or P<0.01). The decreased expression of mRNA and protein and the reduced tyrosine phosphorylation of IRS-2 in CHB patients with insulin resistance inducing impairment of the insulin signal pathway may be one of the mechanisms underlying insulin resistance.

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