O'Doherty R M, Jensen P B, Anderson P, Jones J G, Berman H K, Kearney D, Newgard C B
Gifford Laboratories for Diabetes Research, Marjorie Touchstone Diabetes Center, Department of Biochemistry, Dallas, Texas, USA.
J Clin Invest. 2000 Feb;105(4):479-88. doi: 10.1172/JCI8673.
Glycogen-targeting subunits of protein phosphatase-1, such as protein targeting to glycogen (PTG), direct the phosphatase to the glycogen particle, where it stimulates glycogenesis. We have investigated the metabolic impact of overexpressing PTG in liver of normal rats. After administration of PTG cDNA in a recombinant adenovirus, animals were fasted or allowed to continue feeding for 24 hours. Liver glycogen was nearly completely depleted in fasted control animals, whereas glycogen levels in fasted or fed PTG-overexpressing animals were 70% higher than in fed controls. Nevertheless, transgenic animals regulated plasma glucose, triglycerides, FFAs, ketones, and insulin normally in the fasted and fed states. Fasted PTG-overexpressing animals receiving an oral bolus of [U-(13)C]glucose exhibited a large increase in hepatic glycogen content and a 70% increase in incorporation of [(13)C]glucose into glycogen. However, incorporation of labeled glucose accounted for only a small portion of the glycogen synthesized in PTG-overexpressing animals, consistent with our earlier finding that PTG promotes glycogen synthesis from gluconeogenic precursors. We conclude that hepatic PTG overexpression activates both direct and indirect pathways of glycogen synthesis. Because of its ability to enhance glucose storage without affecting other metabolic indicators, the glycogen-targeting subunit may prove valuable in controlling blood glucose levels in diabetes.
蛋白磷酸酶-1的糖原靶向亚基，如靶向糖原的蛋白（PTG），可将磷酸酶导向糖原颗粒，在那里它刺激糖原生成。我们研究了在正常大鼠肝脏中过表达PTG的代谢影响。在重组腺病毒中给予PTG cDNA后，动物禁食或继续喂养24小时。禁食的对照动物肝脏糖原几乎完全耗尽，而禁食或喂养的PTG过表达动物的糖原水平比喂养的对照动物高70%。然而，转基因动物在禁食和喂养状态下血浆葡萄糖、甘油三酯、游离脂肪酸、酮体和胰岛素的调节正常。接受口服大剂量[U-(13)C]葡萄糖的禁食PTG过表达动物肝脏糖原含量大幅增加，[(13)C]葡萄糖掺入糖原增加70%。然而，标记葡萄糖的掺入仅占PTG过表达动物合成糖原的一小部分，这与我们早期的发现一致，即PTG促进糖异生前体合成糖原。我们得出结论，肝脏PTG过表达激活糖原合成的直接和间接途径。由于其在不影响其他代谢指标的情况下增强葡萄糖储存的能力，糖原靶向亚基可能在控制糖尿病患者血糖水平方面具有价值。
