Challenges and opportunities with glycogen synthase kinase-3 inhibitors for insulin resistance and Type 2 diabetes treatment.
The role of the serine/threonine protein kinase, glycogen synthase kinase-3 (GSK-3), in attenuating the insulin signalling pathway has led to the concept that inhibition of GSK-3 may have therapeutic benefits in the treatment of insulin resistance and Type 2 diabetes. Indeed, various selective GSK-3 inhibitors have been developed recently and have proven to promote insulin-like effects and to act as insulin sensitisers in both in vitro and in vivo systems. GSK-3 inhibition may thus present a new, effective approach for the treatment of insulin resistance and Type 2 diabetes. This review describes the qualifications of GSK-3 as a novel drug-discovery target for Type 2 diabetes and discusses the strategies and challenges in developing small-molecule inhibitors for this important protein kinase.
Eldar-Finkelman
Hagit
H
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Ramat Aviv, Tel-Aviv University, Israel. heldar@post.tau.ac.il
Ilouz
Ronit
R
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D006801:Humans; D007333:Insulin Resistance
D004791:Enzyme Inhibitors; D038362:Glycogen Synthase Kinase 3