Critical role of tissue mast cells in controlling long-term glucose sensor function in vivo

Abstract

Little is known about the specific cells, mediators and mechanisms involved in the loss of glucose sensor function (GSF) in vivo. Since mast cells (MC) are known to be key effector cells in inflammation and wound healing, we hypothesized that MC and their products are major contributors to the skin inflammation and wound healing that controls GSF at sites of sensor implantation. To test this hypothesis we utilized a murine model of continuous glucose monitoring (CGM) in vivo in both normal C57BL/6 mice (mast cell sufficient), as well as mast cell deficient B6.Cg-Kit W-sh / HNihrJaeBsmJ (Sash) mice over a 28 day CGM period. As expected, both strains of mice displayed excellent CGM for the first 7 days post sensor implantation (PSI). CGM in the mast cell sufficient C57BL/6 mice was erratic over the remaining 21 days PSI. CGM in the mast cell deficient Sash mice displayed excellent sensor function for the entire 28 day of CGM. Histopathologic evaluation of implantation sites demonstrated that tissue reactions in Sash mice were dramatically less compared to the reactions in normal C57BL/6 mice. Additionally, mast cells were also seen to be consistently associated with the margins of sensor tissue reactions in normal C57BL/6 mice. Finally, direct injection of bone marrow derived mast cells at sites of sensor implantation induced an acute and dramatic loss of sensor function in both C57BL/6 and Sash mice. These results demonstrate the key role of mast cells in controlling glucose sensor function in vivo.

Role of Interleukin-1/Interleukin-1 Receptor Antagonist Family of Cytokines in Long-Term Continuous Glucose Monitoring In Vivo

“…Glucose sensors were implanted into IL-1Ra~KO, IL-1Ra~OE, or C57BL/6j mice, and CGM was undertaken for a period up to 28 days as described previously. [12][13][14] Blood glucose reference measurements were obtained periodically over the 28-day implantation period, using blood obtained from the tail vein and a FreeStyle blood glucose monitor. The Institutional Animal Care and Use Committee of the University of Connecticut Health Center (Farmington, CT) approved all mice studies.…”

“…13,16 Unfortunately, the specific mediators and mechanisms involved in the loss of sensor function in vivo remains unclear. However, the importance of inflammation in this loss of sensor function is well established.…”

Importance of Interleukin-1 and Interleukin-1 Receptor Antagonist in Short-Term Glucose Sensor Function in Vivo

“…This loss of sensor function in vivo is a result of tissue reactions that include biofouling of the sensor, sensor encapsulation (fibrosis), formation of metabolic barriers by inflammatory cells, 1,2 and loss of vasculature (vessel regression). Unfortunately, the specific mediators and mechanisms involved in the loss of sensor function in vivo remains unclear.…”

Glucose sensing module - is it time to integrate it into real-time perioperative monitoring? An observational pilot study with subcutaneous sensors

“…Even so a gradual decline of accuracy with the time is sometimes observed due to the biofilm formation on the sensor surface, subclinical inflammatory response to a foreign body and formation of reactive oxygen species (ROS) interfering with electrochemical sensing 54,55 . In such case, the sensor should be removed and replaced.…”