The role of glycogen synthase kinase-3 in insulin resistance and type 2 diabetes.
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.
Kaidanovich
Oksana
O
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel-Aviv University, Israel.
Eldar-Finkelman
Hagit
H
D017667:Adipocytes / Q000201:enzymology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000502:physiology; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D008094:Lithium / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
D005230:Fatty Acids, Nonesterified; D006006:Glycogen Synthase; D038362:Glycogen Synthase Kinase 3; D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D008094:Lithium; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; C526292:IRS1 protein, human; C526295:Irs1 protein, mouse