Betatrophin在胰岛素抵抗中的作用及机制研究

胰岛素抵抗在2型糖尿病中起到重要作用。在引起胰岛素抵抗的诸多因素中，胰岛素本身起有关键作用。Betatrophin是一种新发现的在糖代谢中可能起重要作用的分泌蛋白。我们前期的研究显示胰岛素能刺激betatrophin产生并且其水平与胰岛素抵抗相关，但在胰岛素抵抗中的具体作用及机制尚不清楚。本项目拟从以下方面研究betatrophin在高胰岛素引起的胰岛素抵抗中的作用。1）在接受胰岛素注射的小鼠和人群中研究高胰岛素刺激betatrophin分泌的作用及其与胰岛素抵抗的关系。2）在betatrophin表达受抑制和过表达的小鼠模型中，采用胰岛素注射形成高胰岛素血症并造成胰岛素抵抗，以此研究betatrophin在胰岛素抵抗中所起作用。3）通过细胞实验阐明betatrophin导致胰岛素抵抗的分子机制。本研究有助于揭示betatrophin在胰岛素抵抗中所起作用及潜在的治疗靶点。

Insulin resistance, has been assigned a central place in the metabolic disturbances, especially in type 2 diabetes. Among factors induce insulin resistance, an elevated insulin concentration itself can induce or exacerbate insulin resistance. Betatrophin, a novel secreted protein, has been found may play a significant role in glucose metabolism. Previous investigations declared the secretion of betatrophin significantly increased when exposed to high insulin and its level was associated with insulin resistance. However, the regulatory mechanisms of insulin stimulating betatrophin and its role in insulin resistance remain unclear. This project tries to clarify the role of betatrophin in insulin resistance induced by hyperinsulinemia in the following aspects. 1) The effects of insulin stimulating betatrophin will be confirmed in mice and human clinical samples. 2) The role of betatrophin in insulin resistance induced by hyperinsulinemia will be clarified through betatrophin kock-out/transgene mice injected with insulin to induce insulin resistance. 3) the molecular mechanisms of betatrophin in insulin resistance will be explored in vitro cells.The coming study will clarify the overall characters of betatrophin in insulin resistance induced by hyperinsulinemia and explore potential molecular targets for its treatment.