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首页> 外文期刊>Cell metabolism >Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism.
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Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism.

机译：糖原合酶激酶3alpha特异性调节鼠肝糖原代谢。

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摘要

Glycogen synthase kinase 3 comprises two isoforms (GSK-3alpha and GSK-3beta) that are implicated in type II diabetes, neurodegeneration, and cancer. GSK-3 activity is elevated in human and rodent models of diabetes, and various GSK-3 inhibitors improve glucose tolerance and insulin sensitivity in rodent models of obesity and diabetes. Here, we report the generation of mice lacking GSK-3alpha. Unlike GSK-3beta mutants, which die before birth, GSK-3alpha knockout (GSK-3alpha KO) animals are viable but display enhanced glucose and insulin sensitivity accompanied by reduced fat mass. Fasted and glucose-stimulated hepatic glycogen content was enhanced in GSK-3alpha KO mice, whereas muscle glycogen was unaltered. Insulin-stimulated protein kinase B (PKB/Akt) and GSK-3beta phosphorylation was higher in GSK-3alpha KO livers compared to wild-type littermates, and IRS-1 expression was markedly increased. We conclude that GSK-3 isoforms exhibit tissue-specific physiological functions and that GSK-3alpha KO mice are insulin sensitive, reinforcing the potential of GSK-3 as a therapeutic target for type II diabetes.
机译：糖原合酶激酶3包含两个同种型（GSK-3alpha和GSK-3beta），与II型糖尿病，神经变性和癌症有关。在人类和啮齿动物的糖尿病模型中，GSK-3活性升高，而各种GSK-3抑制剂在肥胖和糖尿病的啮齿动物模型中提高了葡萄糖耐量和胰岛素敏感性。在这里，我们报告缺少GSK-3alpha的小鼠的一代。与在出生前死亡的GSK-3beta突变体不同，GSK-3alpha敲除（GSK-3alpha KO）动物是可行的，但显示出增强的葡萄糖和胰岛素敏感性，并伴有脂肪减少。空腹和葡萄糖刺激的肝糖原含量在GSK-3alpha KO小鼠中增加，而肌肉糖原未改变。与野生型同窝仔猪相比，GSK-3alpha KO肝脏中胰岛素刺激的蛋白激酶B（PKB / Akt）和GSK-3beta磷酸化更高，IRS-1表达显着增加。我们得出结论，GSK-3亚型表现出组织特异性的生理功能，并且GSK-3alpha KO小鼠对胰岛素敏感，从而增强了GSK-3作为II型糖尿病治疗靶点的潜力。

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