Characterization of glucose-6-phosphatase in hepatocytes. Effects of amiloride and pentamidine.

The hepatic microsomal glucose-6-phosphatase enzyme is situated inside the lumen of the endoplasmic reticulum and, for normal enzyme activity in vivo, three transport systems are needed for the substrate glucose-6-phosphate and the products phosphate and glucose. Previous studies using isolated microsomes showed that the drugs amiloride and pentamidine do not affect the glucose-6-phosphatase enzyme but can activate the glucose-6-phosphate transport system. Here we demonstrate that, very surprisingly, the addition of pentamidine (and to a lesser extent amiloride) to isolated hepatocytes results in an inhibition of the catalytic subunit of glucose-6-phosphatase.