Insulin-induced increases in the activity of the spontaneously active and ATP . Mg-dependent forms of phosphatase-1 in alloxan-diabetic rat liver

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Abstract
Liver supernatant from normal and alloxan‐diabetic rats was fractionated by DEAE‐cellulose chromatography and the separated phosphoprotein phosphatase fractions were assayed with [32P]histone f2b, [32P]phosphorylase a and [32P]phosphorylase kinase as substrates. In diabetic rat liver, one of the phosphatase fractions found in the normal liver was significantly reduced. This fraction was identified as a mixture of the spontaneously active form and the ATP. Mg‐dependent form of phosphoprotein phosphatase‐1 (Fc) based on sensitivity to inhibitor‐2, substrate specificity, and the fact that it could be activated 42–70% by glycogen synthase kinase‐3 in the presence of ATP · Mg. Further analysis of this fraction showed that liver cytosol from diabetic rats contained 62–79% lower spontaneously active phosphatase‐1 activity and 40–51% lower combined spontaneously active and ATP · Mg‐dependent protein phosphatase‐1 (Fc) activity. Insulin administration increased the spontaneously active and the ATP · Mg‐dependent protein phosphatase‐1 activities approximately 45% and 36%, respectively, in alloxan‐diabetic rats. These data imply that the lower levels of spontaneously active phosphatase‐1 activity in diabetic rat liver cannot be explained by presuming phosphatase‐1 to have been present as Fc, the inactive form. Moreover, insulin restored the total activity of the spontaneously active and activatable forms of phosphatase‐1 to those present in normal liver implying that both forms of phosphatase‐1 activity are under hormonal control.