Details

Autor(en) / Beteiligte

• Weitz, Jonathan

Titel

Paracrine Signaling in the Pancreatic Islet: Mechanisms for Macrophage Maintenance of Tissue Homeostasis

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2018

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Dysfunction or death of the islet’s endocrine cells leads to diabetes, a devastating disease affecting millions worldwide. Islet hormones secreted from endocrine cells are responsible for maintenance of blood glucose levels. However, hormone secretion from beta cells also involves the co-release of pro-inflammatory molecules such as ATP and serotonin. Thus, as a by-product of hormone secretion, islet endocrine cells may activate and interact with the local population of immune cells. The immune system mediates inflammatory responses, but in many tissues, immune cells also provide a homeostatic function. Resident macrophages in the liver (Kupffer Cells), and brain (microglia), for instance, fulfill local roles in immune suppression and tissue repair. These findings suggest a sensitive crosstalk between the local microenvironment and their unique tissue macrophages. These signaling networks have yet to be determined in the pancreatic islet. This thesis project explores these signaling networks. Our data indicate that islet resident macrophages sense locally released ATP by beta cells during high glucose stimulation. We show that the activation of resident macrophages by beta cells through paracrine ATP signaling can be blocked directly by purinergic antagonists. In response to ATP islet macrophages have altered expression profile of matrix remodeling genes. Therefore, islet macrophages act as a local sensor of beta cell activity, and adjust their function accordingly.