Hansen L, Arden K C, Rasmussen S B, Viars C S, Vestergaard H, Hansen T, Møller A M, Woodgett J R, Pedersen O
Steno Diabetes Center and Hagedorn Research Institute, Copenhagen, Denmark.
Diabetologia. 1997 Aug;40(8):940-6. doi: 10.1007/s001250050771.
Activation of glycogen synthesis in skeletal muscle in response to insulin results from the combined inactivation of glycogen synthase kinase-3 (GSK-3) and activation of the protein phosphatase-1, changing the ratio between the inactive phosphorylated state of the glycogen synthase to the active dephosphorylated state. In a search for genetic defects responsible for the decreased insulin stimulated glycogen synthesis seen in patients with non-insulin-dependent diabetes mellitus (NIDDM) and their glucose-tolerant first-degree relatives we have performed mutational analysis of the coding region of the 2 isoforms of GSK-3alpha and GSK-3beta in 72 NIDDM patients and 12 control subjects. No structural changes were detected apart from a few silent mutations. Mapping of the GSK-3alpha to chromosome 19q13.1-13.2 and the GSK-3beta to chromosome 3q13.3-q21 outside known genetic loci linked to NIDDM further makes it unlikely that these genes are involved in the pathogenesis of common forms of NIDDM.
胰岛素作用下，骨骼肌中糖原合成的激活源于糖原合酶激酶-3（GSK-3）的失活与蛋白磷酸酶-1的激活共同作用，从而改变了糖原合酶由无活性的磷酸化状态向有活性的去磷酸化状态的比例。为了寻找导致非胰岛素依赖型糖尿病（NIDDM）患者及其糖耐量正常的一级亲属中胰岛素刺激的糖原合成减少的遗传缺陷，我们对72例NIDDM患者和12名对照受试者的GSK-3α和GSK-3β两种同工型的编码区进行了突变分析。除了一些沉默突变外，未检测到结构变化。GSK-3α定位于19q13.1-13.2染色体，GSK-3β定位于3q13.3-q21染色体，在已知与NIDDM相关的遗传位点之外，这进一步表明这些基因不太可能参与常见形式NIDDM的发病机制。
