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降脂蛋白或可保护胰岛β细胞
作者:小柯机器人 发布时间:2019/11/11 21:29:45

美国康奈尔大学James C. Lo和哈佛大学医学院Jennifer E. Ho等研究人员合作取得一项新成果。他们发现降脂蛋白能保护糖尿病小鼠的β细胞,并与保护人类免受2型糖尿病有关。相关论文2019年11月7日在线发表于《自然—医学》。

研究人员表示,2型糖尿病的特征是胰岛素抵抗以及胰岛β细胞质量和功能的逐渐丧失。目前,尚无获得证实的预防β细胞丧失疗法,其中一些疗法(即胰岛素促分泌素)与加速β细胞衰竭有关,从而限制了它们在2型糖尿病中的应用。脂肪因子降脂蛋白/补体因子D控制补体旁路途径和补体成分C3a的产生,其作用是增强β细胞胰岛素的分泌。

与其他胰岛素促分泌素相反,研究人员发现糖尿病db/db小鼠中的降脂蛋白的慢性补充可改善高血糖症并增加胰岛素水平,同时通过阻止去分化和死亡来保护β细胞。从机理上讲,研究人员发现降脂蛋白/C3a降低了磷酸酶Dusp26的表达。Dusp26在β细胞中的强制表达会降低β细胞核心身份基因的表达,并对细胞死亡敏感。相反,DUSP26的药理抑制作用可改善糖尿病小鼠的高血糖症,并保护人胰岛细胞免受细胞死亡。关于人体健康,研究人员发现,在调整了体重指数(BMI)之后,中年成年人中循环脂肪含量的升高与未来罹患糖尿病的风险显著降低有关。总体而言,这些数据表明,用降脂蛋白/C3a和DUSP26指导的疗法可能是一种实现β细胞健康的新方法,从而治疗和预防2型糖尿病。

附:英文原文

Title: Adipsin preserves beta cells in diabetic mice and associates with protection from type 2 diabetes in humans

Author: Nicols Gmez-Banoy, J. Sawalla Guseh, Ge Li, Alfonso Rubio-Navarro, Tong Chen, BreAnne Poirier, Gregory Putzel, Carolina Rosselot, Maria A. Pabn, Joo Paulo Camporez, Vijeta Bhambhani, Shih-Jen Hwang, Chen Yao, Rachel J. Perry, Sushmita Mukherjee, Martin G. Larson, Daniel Levy, Lukas E. Dow, Gerald I. Shulman

Issue&Volume: 2019-11-07

Abstract: Type 2 diabetes is characterized by insulin resistance and a gradual loss of pancreatic beta cell mass and function1,2. Currently, there are no therapies proven to prevent beta cell loss and some, namely insulin secretagogues, have been linked to accelerated beta cell failure, thereby limiting their use in type 2 diabetes3,4. The adipokine adipsin/complement factor D controls the alternative complement pathway and generation of complement component C3a, which acts to augment beta cell insulin secretion5. In contrast to other insulin secretagogues, we show that chronic replenishment of adipsin in diabetic db/db mice ameliorates hyperglycemia and increases insulin levels while preserving beta cells by blocking dedifferentiation and death. Mechanistically, we find that adipsin/C3a decreases the phosphatase Dusp26; forced expression of Dusp26 in beta cells decreases expression of core beta cell identity genes and sensitizes to cell death. In contrast, pharmacological inhibition of DUSP26 improves hyperglycemia in diabetic mice and protects human islet cells from cell death. Pertaining to human health, we show that higher concentrations of circulating adipsin are associated with a significantly lower risk of developing future diabetes among middle-aged adults after adjusting for body mass index (BMI). Collectively, these data suggest that adipsin/C3a and DUSP26-directed therapies may represent a novel approach to achieve beta cell health to treat and prevent type 2 diabetes. Targeting the adipokine adipsin and its downstream pathway may provide an approach for preservation of beta cell loss in type 2 diabetes.

DOI: 10.1038/s41591-019-0610-4

Source:https://www.nature.com/articles/s41591-019-0610-4

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex