Targeting glycogen kinase-3 (GSK-3) in the treatment if Type 2 diabetes

被引:12
|
作者
MacAulay, Katrina [1 ]
Woodgett, James R. [1 ]
机构
[1] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada
基金
加拿大健康研究院;
关键词
diabetes; glucose tolerance; glycogen synthase kinase-3; insulin; metabolism;
D O I
10.1517/14728222.12.10.1265
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: In spite of its rather specific name, glycogen synthase kinase-3 (GSK-3) is an eclectic cellular regulator that modulates an array of processes from nuclear transcription, to neurological functions and metabolism. The enzyme is also a focal point for diverse signaling pathways that act to suppress its activity. Objectives: To review recent evidence supporting the important role GSK-3 plays in glucose homeostasis and discuss the therapeutic potential of inhibiting this enzyme in the treatment of diabetes and insulin resistance. Results/conclusion: Despite its pleiotropic nature, GSK-3 has significant promise as a target for diabetes due to functional partitioning of the enzyme, tissue-selectivity and acute dosage-dependency of effects of inhibition, suggesting useful therapeutic windows.
引用
收藏
页码:1265 / 1274
页数:10
相关论文
共 50 条
  • [1] Glycogen synthase kinase-3 (GSK-3): A kinase with exceptional therapeutic potential
    Benbow, JW
    Helal, CJ
    Kung, DW
    Wager, TT
    ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 40, 2005, 40 : 135 - 147
  • [2] Glycogen Synthase Kinase-3 (GSK-3) Inhibitors for the Treatment of Alzheimer's Disease
    Medina, Miguel
    Avila, Jesus
    CURRENT PHARMACEUTICAL DESIGN, 2010, 16 (25) : 2790 - 2798
  • [3] Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy and Imaging
    Pandey, Mukesh K.
    DeGrado, Timothy R.
    THERANOSTICS, 2016, 6 (04): : 571 - 593
  • [4] Expression and localization of glycogen synthase kinase-3 (GSK-3) in mouse
    Yao, HB
    Shaw, PC
    Wan, DCC
    FASEB JOURNAL, 2001, 15 (04): : A547 - A547
  • [5] Glycogen synthase kinase-3 (GSK-3) inhibitors reach the clinic
    Medina, Miguel
    Castro, Ana
    CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT, 2008, 11 (04) : 533 - 543
  • [6] Inhibitory phosphorylation of glycogen synthase kinase-3 (GSK-3) in response to lithium - Evidence for autoregulation of GSK-3
    Zhang, F
    Phiel, CJ
    Spece, L
    Gurvich, N
    Klein, PS
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (35) : 33067 - 33077
  • [7] Regulation of Autophagy by the Glycogen Synthase Kinase-3 (GSK-3) Signaling Pathway
    Pan, Hsuan-Yeh
    Valapala, Mallika
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (03)
  • [8] Glycogen synthase kinase-3β (GSK-3β) and its dysregulation in glioblastoma multiforme
    Atkins, R. J.
    Stylli, S. S.
    Luwor, R. B.
    Kaye, A. H.
    Hovens, C. M.
    JOURNAL OF CLINICAL NEUROSCIENCE, 2013, 20 (09) : 1185 - 1192
  • [9] A Novel Potent and Selective Inhibitor of Glycogen Synthase Kinase-3 (GSK-3)
    Noori, Mahboubeh S.
    Courreges, Maria C.
    Bergmeier, Stephen C.
    McCall, Kelly D.
    Goetz, Douglas J.
    FASEB JOURNAL, 2018, 32 (01):
  • [10] A Noncatalytic Domain of Glycogen Synthase Kinase-3 (GSK-3) Is Essential for Activity
    Buescher, Jessica L.
    Phiel, Christopher J.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (11) : 7957 - 7963