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    MICRORNA AS A BIOMARKER OF PANCREATIC ISLET BETA-CELL ENGAGEMENT
    5.
    发明申请
    MICRORNA AS A BIOMARKER OF PANCREATIC ISLET BETA-CELL ENGAGEMENT 审中-公开
    MICRORNA作为PANCREATIC ISLET BETA-CELL参与的生物标记

    公开(公告)号：US20120034608A1

    公开(公告)日：2012-02-09

    申请号：US13263427

    申请日：2010-04-05

    申请人： Yun-Ping Zhou ,  Andrew D. Howard ,  Jin Shang

    发明人： Yun-Ping Zhou ,  Andrew D. Howard ,  Jin Shang

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/686 ,  C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/136 ,  C12Q2525/207 ,  C12Q2521/107

    摘要： MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and which play important roles in many cell types, including as described herein, the pancreatic β-cell. Glucagon like peptide-1 (GLP-1), a hormone released from intestinal L-cells following meal intake, exerts pleiotropic effects on β-cell function including raising intracellular cAMP levels and now represents an important therapy for type 2 diabetes. Expression of miR-132 and miR212 is upregulated by CREB protein in response increased cAMP levels in the cell; therefore, methods for detecting and evaluating β-cell engagement by GLP-1 receptor agonists by monitoring miR-132 and miR-212 expression in a subject is described. The methods herein are particularly useful in the context of longitudinal clinical trials, such as those designed for testing the durability of any single or combination therapy in type 2 diabetes populations. Because the expression of these miRNAs is not affected by glucose, fatty acid, insulin, or β-cell function, monitoring miR-132 and miR-212 expression can be used to monitor the efficacy of any agent that effects an increase cAMP in β-cells. Such agents include for example, GLP-1, glucagon, GPR-119, and GIP receptor agonists; dipeptidyl peptidase IV (DPP IV) inhibitors; and phosphodiesterase inhibitors.

    摘要翻译： 微小RNA（miRNA）是调节基因表达的短非编码RNA，并且在许多细胞类型中起重要作用，包括本文所述的胰腺细胞。 胰高血糖素样肽-1（GLP-1）是膳食摄入后从肠道L细胞释放的激素，对细胞功能具有多效性，包括提高细胞内cAMP水平，现在代表了2型糖尿病的重要疗法。 miR-132和miR212的表达由CREB蛋白上调，响应细胞中cAMP水平升高; 因此，描述了通过监测受试者中的miR-132和miR-212表达来检测和评估GLP-1受体激动剂的细胞参与的方法。 本文的方法在纵向临床试验的背景下特别有用，例如设计用于测试2型糖尿病人群中任何单一或联合疗法的耐久性的那些。 因为这些miRNA的表达不受葡萄糖，脂肪酸，胰岛素或细胞功能的影响，监测miR-132和miR-212表达可用于监测影响增加cAMP的任何试剂的功效 ;-细胞。 这些药剂包括例如GLP-1，胰高血糖素，GPR-119和GIP受体激动剂; 二肽基肽酶IV（DPP IV）抑制剂; 和磷酸二酯酶抑制剂。