Zhou Heather, Song Xiaomin, Briggs Mike, Violand Bernard, Salsgiver William, Gulve Eric A, Luo Yi
Department of Cardiovascular Diseases, and Global Biotechnology Pharmacia Corporation, USA.
Biochem Biophys Res Commun. 2005 Dec 16;338(2):793-9. doi: 10.1016/j.bbrc.2005.10.007. Epub 2005 Oct 11.
Adiponectin plays important roles in regulating insulin sensitivity and atherogenesis. Adiponectin has been shown to suppress hepatic glucose production in rodents. It has not been reported whether ectopically expressed adiponectin could regulate glucose metabolism in cultured hepatocyte-like cells. In the current study, the effect of adiponectin on glucose production was analyzed by ectopically expressing the protein in hepatoma H4IIE cells using an adenovirus delivery system to generate both human full-length and the globular domain of the protein. Expression of adiponectin in hepatoma H4IIE cells, in the absence of insulin, suppressed expression of the genes encoding glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, rate-limiting enzymes in the gluconeogenic pathway. Furthermore, expression of adiponectin in H4IIE cells suppressed glucose production from lactate and pyruvate. Purified recombinant human adiponectin also reduced glucose production in H4IIE cells and in rat primary hepatocytes in the absence of insulin. These data suggest that adiponectin protein could exert its function independent of the presence of insulin in these culture systems.
脂联素在调节胰岛素敏感性和动脉粥样硬化形成中发挥着重要作用。在啮齿动物中，脂联素已被证明可抑制肝脏葡萄糖生成。异位表达的脂联素是否能调节培养的类肝细胞中的葡萄糖代谢尚未见报道。在本研究中，通过腺病毒递送系统在肝癌H4IIE细胞中异位表达人全长脂联素及其球状结构域蛋白，分析脂联素对葡萄糖生成的影响。在无胰岛素的情况下，脂联素在肝癌H4IIE细胞中的表达抑制了糖异生途径中限速酶葡萄糖-6-磷酸酶和磷酸烯醇式丙酮酸羧激酶编码基因的表达。此外，脂联素在H4IIE细胞中的表达抑制了乳酸和丙酮酸生成葡萄糖。纯化的重组人脂联素在无胰岛素的情况下也降低了H4IIE细胞和大鼠原代肝细胞中的葡萄糖生成。这些数据表明，在这些培养系统中，脂联素蛋白可以在无胰岛素的情况下发挥其功能。
