Elucidation of pathophysiological roles of Wnt5b gene susceptible to type 2 diabetes in glucose metabolism in liver

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Wnt/β-catenin signaling is reported to be associated with insulin secretion and adipocyte differentiation. However physiological roles in liver have remained unknown. Recently, it has been reported that Wnt5b gene, one of the Wnt family, is susceptible to type2 diabetes and regulates 9-catenin signaling negatively. In order to investigate some roles of Wnt/β-catenin signaling and Wnt5b gene in liver we examined whether activation of β-catenin signaling can affect glucose metabolism using primary rat hepatocytes. lithium chloride phosphorylated GSK-3f3 and reduced the gene expression levels of PEPCK and G6Pase that are associated with gluconeogenesis. Additionally, we did ipGTT in mice and examined the expression level of Wnt5b gene in liver of db/db mice. The result of ipGTT showed that the expression level of Wnt5b gene was transiently increased after glucose loading and Wnt5b gene expression in live of db/db mice was increased compared with control mice. From these results, it could be hypothesized that Wnt/β-catenin signaling has pathophyisological roles in hepatic glucose metabolism. Therefore, we overexpressed mouse Wnt5b gene in mouse liver using adenovirus vector However no remarkable changes in Wnt5b-overexpressed mice were found in both fasting glucose and after glucose loading compared with control mice and we did not find direct effects of Wnt5b gene on hepatic glucose metabolism in vivo model However, previous reports showed that Wnt/β-catenin signaling was associated with lipid metabolism in liver. Therefore Wnt/β-catenin signaling may have indirect effects on onset or/and progression of diabetes by regulating lipid metabolism and it is important to clear pathophyisological roles of Wnt5b gene in lipid metabolism.