The P2X7 receptor and pannexin-1 are involved in glucose-induced autocrine regulation in ?-cells.

ABSTRACT: Extracellular ATP is an important short-range signaling molecule that promotes various physiological responses virtually in all cell types, including pancreatic ?-cells. It is well documented that pancreatic ?-cells release ATP through exocytosis of insulin granules upon glucose stimulation. We hypothesized that glucose might stimulate ATP release through other non-vesicular mechanisms. Several purinergic receptors are found in ?-cells and there is increasing evidence that purinergic signaling regulates ?-cell functions and survival. One of the receptors that may be relevant is the P2X7 receptor, but its detailed role in ?-cell physiology is unclear. In this study we investigated roles of the P2X7 receptor and pannexin-1 in ATP release, intracellular ATP, Ca2+ signals, insulin release and cell proliferation/survival in ?-cells. Results show that glucose induces rapid release of ATP and significant fraction of release involves the P2X7 receptor and pannexin-1, both expressed in INS-1E cells, rat and mouse ?-cells. Furthermore, we provide pharmacological evidence that extracellular ATP, via P2X7 receptor, stimulates Ca2+ transients and cell proliferation in INS-1E cells and insulin secretion in INS-1E cells and rat islets. These data indicate that the P2X7 receptor and pannexin-1 have important functions in ?-cell physiology, and should be considered in understanding and treatment of diabetes.

SUBMITTER: Tozzi M 

PROVIDER: S-EPMC5997690 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature