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In 1975, Arion and colleagues discovered that hepatocytes release glucose into the bloodstream in response to hypoglycaemia using the glucose-6-phosphatase (G6Pase) system. This system is in the endoplasmic reticulum (ER) and is composed of two functionally linked proteins, a G6P transporter subunit (G6PT) and a catalytic subunit called G6P phosphatase (G6Pase). The G6PT subunit promotes the storage of G6P inside the ER, while G6Pase, which has its catalytic domain in the reticular lumen, hydrolyses G6P to yield free glucose + phosphate. The free glucose stored in the reticular lumen can be transported to the cytosol and from there to the extracellular space in hypoglycaemic conditions by a direct mechanism that has not yet been established, but eventually by glucose transporters (GLUTs).


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