Inflammation and Glucose Sensor Function

描述（由申请人提供）：背景：在开发用于糖尿病患者的可植入葡萄糖传感器方面已经投入了大量的努力，但是由于功能丧失，目前的传感器仅持续数小时至数天。传感器功能的丧失部分是葡萄糖传感器周围炎症、纤维化和血管退化的组织反应三联体的结果。由于肥大细胞在所有这些过程中起着关键作用，我们提出了以下假设格兰特假说：肥大细胞及其活化产物通过释放直接生物污染葡萄糖传感器的试剂，以及释放促炎剂（例如，肥大细胞衍生的血管活性和趋化因子），其促进炎症和组织损伤，从而导致体内短期和长期的传感器功能丧失。研究设计：使用我们最近开发的可植入葡萄糖传感器的小鼠模型，我们将确定肥大细胞的缺失和/或抑制的影响，以及传感器在体内的功能。具体目标：具体目标1：确定肥大细胞和肥大细胞活化在体内葡萄糖传感器功能丧失和寿命中的作用具体目的2：确定肥大细胞（MC）和MC产物对体外葡萄糖传感器功能的直接影响具体目的3：鉴定体内和体外导致葡萄糖传感器功能丧失的肥大细胞衍生因子。

DESCRIPTION (provided by applicant): Background: Significant effort has been invested in developing implantable glucose sensors for diabetics, but current sensors last only hrs to days due to loss of function. This loss of sensor function is in part the result of the tissue response triad of inflammation, fibrosis and vessel regression surrounding the glucose sensor. Since mast cells play a key role in all these processes we have developed the following hypothesis Grant Hypothesis: Mast cells, and their activation products, directly and indirectly contribute to the lose of glucose sensor function in vivo, by releasing agents that directly biofoul glucose sensors, as well as by releasing pro-inflammatory agents (e.g. mast cell derived vasoactive and chemotactic factors) that promote inflammation and tissue injury, and thereby are responsible for loss of sensor function both short term and long term in vivo. Study Design: Using our recently developed mouse model of implantable glucose sensors we will determine the impact of deletion and or inhibition of mast cells and the production on sensor function in vivo. Specific Aims: SPECIFIC AIM 1: To Determine the Role of Mast Cells and Mast Cell Activation, in the Loss of Glucose Sensor Function and Lifespan in Vivo SPECIFIC AIM 2: To Determine the Direct Impact of Mast Cells (MCs), and MCs Products, on Glucose Sensor Function in Vitro SPECIFIC AIM 3: To Identify Mast Cell Derived Factors that Contribute to the Loss of Glucose Sensor Function in Vivo and in Vitro.