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

来源：

EXPERT OPINION ON THERAPEUTIC TARGETS | 2008年 / 12卷 / 10期

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

页码：1265 / 1274

页数：10

共 50 条

[21] Inhibiting glycogen synthase kinase-3 (GSK-3) prevents the development of myeloma bone disease
Abdul, N.
Stoop, W.
Koopman, W.
Djerbi, M.
Chantry, A. D.
Evans, H.
Vanderkerken, K.
Croucher, P. I.
BONE, 2009, 44 : S53 - S54
[22] A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3β (GSK-3β) and mediates protein kinase A-dependent inhibition of GSK-3β
Tanji, C
Yamamoto, H
Yorioka, N
Kohno, N
Kikuchi, K
Kikuchi, A
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (40) : 36955 - 36961
[23] 3-anilino-4-arylmaleimides: Potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3)
Smith, DG
Buffet, M
Fenwick, AE
Haigh, D
Ife, RJ
Saunders, M
Slingsby, BP
Stacey, R
Ward, RW
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (05) : 635 - 639
[24] Glycogen synthase kinase-3 beta (GSK-3/β) inhibitors as radioprotectors of hippocampal neurons in the developing brain
Thotala, D.
Hallahan, D. E.
Yazlovitskaya, E. M.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2007, 69 (03): : S124 - S125
[25] 2,5-Diaminopyrimidines and 3,5-disubstituted azapurines as inhibitors of glycogen synthase kinase-3 (GSK-3)
Lum, Christopher
Kahl, Jeff
Kessler, Linda
Kucharski, Jeff
Lundstrom, Jan
Miller, Stephen
Nakanishi, Hiroshi
Pei, Yazhong
Pryor, Kent
Roberts, Edward
Sebo, Lubomir
Sullivan, Robert
Urban, Jan
Wang, Zhijun
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (12) : 3578 - 3581
[26] Binding of glycogen synthase kinase-3 (GSK-3) to immobilized axin: A single step purification method for assay of GSK-3 activity in sperm extracts
Shenoy, SPRS
Jack, S
Vijayaraghavan, S
BIOLOGY OF REPRODUCTION, 2003, 68 : 171 - 172
[27] Inhibition by lithium of glycogen synthase kinase-3 (GSK-3): Possible mechanism of therapeutic action of lithium
Herve, D.
EUROPEAN PSYCHIATRY, 2014, 29 (08) : 669 - 670
[28] Characterization of Maleimide-Based Glycogen Synthase Kinase-3 (GSK-3) Inhibitors as Stimulators of Steroidogenesis
Gunosewoyo, Hendra
Midzak, Andrew
Gaisina, Irina N.
Sabath, Emily V.
Fedolak, Allison
Hanania, Taleen
Brunner, Dani
Papadopoulos, Vassilios
Kozikowski, Alan P.
JOURNAL OF MEDICINAL CHEMISTRY, 2013, 56 (12) : 5115 - 5129
[29] Pharmacological inhibitors of cyclin-dependent kinases (CDKS) and glycogen synthast kinase-3 (GSK-3).
Meijer, L
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2003, 226 : U460 - U460
[30] Mitochondrial fragmentation induced by UV and ischemia. Role of glycogen synthase kinase-3 (GSK-3)
Plotnikov, E. Y.
Vasileva, A. K.
Shashkova, A. A.
Zorov, D. B.
FEBS JOURNAL, 2007, 274 : 205 - 205

← 1 2 3 4 5 →