Mori H, Stone K, Mott D M
Clinical Diabetes and Nutrition Section, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016.
Am J Physiol. 1994 Apr;266(4 Pt 1):E574-82. doi: 10.1152/ajpendo.1994.266.4.E574.
Reduced type 1 protein phosphatase (PP-1) activity in human muscle extracts may contribute to the reduced insulin-stimulated glycogen synthase activity associated with insulin resistance for glucose disposal in humans. Because inactive forms of PP-1 can be activated with trypsin plus Mn2+, these reagents were used to compare the PP-1 activities in skeletal muscle extracts before and after separation into cytosolic and glycogen microsomal (GM) fractions. PP-1 activities were reduced in the GM fraction from insulin-resistant subjects (54 +/- 2 vs. 61 +/- 1, P < 0.01) but, in contrast to our previously published results, were elevated in the extract (33 +/- 6 vs. 18 +/- 3, P < 0.05). Recombination of the cytosol and GM fractions (reconstituted extract) demonstrated that the low extract PP-1 activities could only be regenerated when the GM fraction from insulin-sensitive subjects was recombined with cytosol from either group. The results indicate that the elevated PP-1 activity observed in extracts of insulin-resistant compared with insulin-sensitive subjects is caused by an inhibitor of extract PP-1 activity that sediments with the GM pellet and is more active in the insulin-sensitive subjects.
人体肌肉提取物中1型蛋白磷酸酶（PP - 1）活性降低，可能导致胰岛素刺激的糖原合酶活性降低，而这与人体葡萄糖处理过程中的胰岛素抵抗有关。由于PP - 1的无活性形式可被胰蛋白酶加Mn2+激活，因此使用这些试剂来比较骨骼肌提取物在分离为胞质和糖原微粒体（GM）部分前后的PP - 1活性。胰岛素抵抗受试者的GM部分中PP - 1活性降低（54±2对61±1，P < 0.01），但与我们之前发表的结果相反，提取物中的PP - 1活性升高（33±6对18±3，P < 0.05）。胞质和GM部分重组（重组提取物）表明，只有当胰岛素敏感受试者的GM部分与两组中任何一组的胞质重组时，提取物中低PP - 1活性才能恢复。结果表明，与胰岛素敏感受试者相比，胰岛素抵抗受试者提取物中观察到的PP - 1活性升高是由一种与GM沉淀一起沉降的提取物PP - 1活性抑制剂引起的，且该抑制剂在胰岛素敏感受试者中更具活性。
