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.
| Wisniewski, Natalie A; Klueh, Uli; Stenken, Julie (2011) Interstitial fluid physiology as it relates to glucose monitoring technologies: symposium introduction. J Diabetes Sci Technol 5:579-82 |
| Klueh, Ulrike; Kaur, Manjot; Qiao, Yi et al. (2010) Critical role of tissue mast cells in controlling long-term glucose sensor function in vivo. Biomaterials 31:4540-51 |
| Klueh, Ulrike; Liu, Zenghe; Feldman, Ben et al. (2010) Importance of interleukin-1 and interleukin-1 receptor antagonist in short-term glucose sensor function in vivo. J Diabetes Sci Technol 4:1073-86 |
