Figure 8.

Cell model for autocrine purinergic signaling in β-cells. Glucose enters the cell and is metabolized to ATP. On left side of the cell (in blue) we show the well-established events: closure of ATP-sensitive K⁺ channels leading to cell membrane depolarization, opening of voltage-sensitive Ca²⁺ channels and influx of Ca²⁺ that triggers exocytosis of insulin-containing granules. Granules also contain ATP which is accumulated by VNUT. Our study on INS-1E cells shows (in green) that ATP is also released via pannexin-1 (Panx1) and the process is regulated by the P2X7R. Extracellular ATP binds to the receptor and causes further influx of Ca²⁺ and potentiation of insulin secretion. The resulting amplification of the Ca²⁺ signal promotes additional exocytosis of secretory granules. The P2X7 receptor also regulates β-cell proliferation/survival. ATP can also be released by cell volume/stress, but since these have no effect on cell proliferation, one or more of the steps in the glucose uptake – metabolism – Panx1 - P2X7R – chain are missing.