Protein phosphatase-1 and -2A, kinase F A, and casein kinase II in skeletal muscle of streptozotocin diabetic rats

Abstract

Protein phosphatase-1 (PP-1) and -2A (PP-2A), two regulatory subunits of PP-1, the glycogen-binding subunit G and inhibitor-2 (I-2), kinase F A, and casein kinase II (CK-II) were investigated in skeletal muscle of diabetic rats 2 days after Streptozotocin injection. F A and CK-II activate PP-1 in vitro and might be involved in the activation of PP-1 by insulin. Following muscle fractionation we found that (1) diabetes decreased both basal and trypsin-stimulated PP-1 activities; the decrease was more significant in the glycogen-bound and microsomal fractions than in the cytosol (cytosolic PP-1 decreased as specific activity but not as activity/g of muscle); also PP-2A was lower in diabetic cytosols; (2) less G was immunoprecipitated from diabetic glycogen-bound fractions compared to controls, while I-2 was not significantly changed; (3) diabetes decreased also F A (assayed as PP-1 activator) and CK-II (assayed using a synthetic peptide as substrate); (4) diabetes did not have any effect on phosphorylase ( a + b) activity in the glycogen-bound fraction. Altogether the data show that acute diabetes decreased PP-1, one of its regulatory subunits and two potentially physiological regulators of PP-1, in addition to PP-2A. This may indicate that insulin is responsible for the long-term regulation of the same enzymes that are also under acute insulin control.