Abstract
Glycogen synthase kinase-3 (GSK-3) is a ubiquitous cytosolic serine/threonine protein kinase that has been implicated in multiple receptor-mediated intracellular processes. Its unique feature, which distinguishes it from other protein kinases, is that it is constitutively active in resting conditions and acts as a suppressor of signalling pathways. The fact that the function of two key targets of insulin action, glycogen synthase and insulin receptor substrate-1, are suppressed by GSK-3, as well as the fact that GSK-3 activity is higher in diabetic tissues, makes it a promising drug discovery target for insulin resistance and Type 2 diabetes. Thus, the development of GSK-3 inhibitors has received attention as an attempt to control both the spread of the disease and its severity.
MeSH terms
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Adipocytes / enzymology
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Animals
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Diabetes Mellitus, Experimental / enzymology
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Diabetes Mellitus, Type 2 / drug therapy
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Diabetes Mellitus, Type 2 / enzymology*
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Fatty Acids, Nonesterified / metabolism
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Glycogen Synthase / metabolism
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Glycogen Synthase Kinase 3 / antagonists & inhibitors*
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Glycogen Synthase Kinase 3 / physiology
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Humans
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Hypoglycemic Agents / pharmacology*
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Hypoglycemic Agents / therapeutic use
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Insulin / physiology
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Insulin Receptor Substrate Proteins
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Insulin Resistance
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Lithium / pharmacology
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Mice
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Mice, Knockout
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Obesity / enzymology
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Phosphatidylinositol 3-Kinases / physiology
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Phosphoproteins / physiology
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Phosphorylation / drug effects
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Protein Kinase Inhibitors / pharmacology*
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Protein Kinase Inhibitors / therapeutic use
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Protein Processing, Post-Translational / drug effects
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Protein Serine-Threonine Kinases / physiology
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-akt
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Receptor, Insulin / physiology
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Signal Transduction / drug effects
Substances
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Fatty Acids, Nonesterified
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Hypoglycemic Agents
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IRS1 protein, human
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Insulin
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Insulin Receptor Substrate Proteins
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Irs1 protein, mouse
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Phosphoproteins
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins
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Lithium
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Glycogen Synthase
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Receptor, Insulin
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Glycogen Synthase Kinase 3