Erythropoietin receptor and glucose metabolism

促红细胞生成素受体与葡萄糖代谢

• 批准号: 8157974
• 负责人: Constance Noguchi
• 金额: $ 35.17万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8157974
• 关键词: Erythropoietin Receptor; glucose metabolism

Erythropoietin, a cytokine made in the kidney, has proven to be effective therapy for anemia in patients with end-stage renal disease. The tissue distribution and regulation of gene expression for erythropoietin and its receptor reveal important insight on erythropoietin induction by hypoxia, on its role in mature red cell production and its activity in non-hematopoietic tissues. Erythropoietin acts primarily to regulate blood hemoglobin through the formation of mature red blood cells and binds to its receptor on the surface of erythroid progenitor cells to promote erythropoiesis by preventing apoptosis and stimulating proliferation and differentiation. Mice that lack erythropoietin or its receptor die in utero from severe anemia. To determine the role of endogenous erythropoietin beyond erythropoiesis, we examined mice with erythropoietin receptor expression restricted to hematopoietic tissue. These animals survived through adulthood with normalized erythroid differentiation and hematocrit, and exhibited no gross morphologic deformation. We observed that these mice exhibit an age dependent obesity with an increase in body weight up to 50% greater than that of wild type animals at 12 months. These mice eventually became insulin resistance with a significant increase in white fat. Erythropoietin also affected adipogenesis in culture. These observations suggest that erythropoietin may contribute to maintaining fat mass accumulation and provide new insight to the consequence of erythropoietin activity in non-hematopoietic cells.

红细胞生成素是一种肾脏制造的细胞因子，已证明是末期肾脏疾病患者贫血的有效疗法。促红细胞生成素及其受体的基因表达的组织分布和调节揭示了缺氧对促红细胞生成素诱导的重要见解，其在成熟的红细胞生产中的作用及其在非杂造组织中的活性。促红细胞生成素主要起作用，通过成熟的红细胞形成来调节血液白细胞蛋白，并结合其在红细胞祖细胞表面的受体与受体结合，从而通过预防细胞凋亡，刺激增殖和差异来促进红细胞生成。缺乏红细胞生成素或其受体的小鼠因严重的贫血在子宫内死亡。 为了确定内源性促红细胞生成素以外的促红细胞生成的作用，我们检查了以促红细胞生成素受体表达仅限于造血组织的小鼠。这些动物在成年期幸存下来，并具有归一化的红细胞分化和血细胞比容，并且没有表现出粗大的形态变形。我们观察到这些小鼠表现出年龄依赖的肥胖症，体重的增加高达50％，比野生型动物在12个月时的体重高出50％。这些小鼠最终变得胰岛素耐药性，白脂肪显着增加。红细胞生成素还影响培养中的脂肪形成。 这些观察结果表明，促红细胞生成素可能有助于维持脂肪量的积累，并为非造成毛细血管细胞中红细胞生成素活性的后果提供新的见解。