| Objective:Chemerin is a recently discovered heptoadipokine that highly expressed in adipose tissue and liver, chemerin has dual roles in metabolic syndrome and inflammation, and is a ligand of the G-coupled receptor cmklrl. Chemerin could bind to cmklrl on immature dendritic cells and macrophages leading to their recruitment to lymphoid organs and sites of injury. Chemerin was strongly expressed in the human pancreas, chemerin and its receptor were detected in the β-cells of the isltes in mice. Chemerin could regulate hepatic glucose production and muscle glucose uptake, the expression of chemerin in β-cells was regulated depending on the metabolic status, suggested that locally produced chemerin may function in an autocrine/paracrine manner, β-cells may be a direct target for chemerin. Studies using isolated islets and perfused pancreas revealed impaired glucose-dependent insulin secretion(GSIS) in chemerin-deficient mice, conversely, chemerin(+/+) mice revealed enhanced GSIS and improved glucose tolerance, suggested that chemerin regulates β-cell function and plays an important role in glucose homeostasis in a tissue-dependent manner. The expression of chemerin was significantly downregulated in db/db mice and streptozotocin(STZ)-treated diabetic mice compaired with corresponding control mice. TNF-α is a potent regulator of chemerin that upregulates expression of chemerin in adipocyte. Thiazolidinediones can also induce expression of chemerin in adipocyte, and improve the inhibitory effect of IL-6on chemerin expression, so chemerin may be the target gene of TZD to improve insulin sensitivity. A recent study revealed that individuals with high chemerin serum levels coupled with low circulating adiponectin were at significantly increased risk of metabolic syndrome, suggested that chemerin and adiponectin may reciprocally participate in the development of metabolic syndrome. This study aims to investigate the effect of thiazolidinediones on expression of chemerin, cmklrl, tumor necrosis factor-alpha mRNA in liver and serum adiponectin level of diabetic rat model.Methods:Murine diabetic models were induced with STZ.Rats were randomized into normal control group, diabetes group and pioglitazone group. After successful modeling, the pioglitazone concentrations of15mg/d were given to rats of pioglitazone group according to1kg of rat body weight.Rats were sacrificed after8weeks of experiments. At the same time, the liquid nitrogen frozen specimens from liver were taken to use to analyze expressions of chemerin, cmklrl and tumor necrosis factor-alpha mRNA by the method of real-time quantitative PCR. Serum adiponectin level was measured using ELISA.Results:Results of real-time quantitative PCR showed that chemerin mRNA was highly expressed in liver of SD rats, chemerin mRNA expression levels were higher than housekeeping gene β-actin in normal control group, diabetes group and pioglitazone group. Expressions of chemerin mRNA was significantly lower in diabetes group than that of normal control group and pioglitazone group (P<0.017) As receptor of chemerin, cmklrl was also detected in liver of SD rats, no significant difference was found in expressions of cmklrl mRNA between three groups. The expression of TNF-α mRNA was higer in diabetes group than that of normal control group(P<0.017). Serum adiponectin levels of diabetes group and pioglitazone group were lower than normal control group, and pioglitazone group showed higher level of serum adiponectin compared with diabetes group(P<0.05).Conclusion:The expression of TNF-α mRNA was upregulated in liver of diabetes group. Pioglitazone may improving insulin sensitivity of liver by upregulating expression of chemerin mRNA in diabetic rats. There were no significant difference in expressions of cmklrl mRNA in liver between normal control group, diabetes group and pioglitazone group. Chemerin may be a target gene of thiazolidinediones to promoting insulin sensitivity,and reduction of TNF-α expression potentially contribute to effects of thiazolidinediones on improve insulin resistance and inflammatory damage in liver. Pioglitazone can promote circulating adiponectin levels of diabetic rats. |
PDF Full Text Request