Targeting glycogen synthase kinase-3 in insulin signalling.
The renewed interest in an enzyme first discovered over 25 years ago stems from the potential of inhibitors of this enzyme to treat conditions as diverse as diabetes, Alzheimer's disease, stroke and bipolar disorder, and even to enhance the repopulating capacity of transplanted haematopoietic stem cells. The emergence of the first few potent and specific glycogen synthase kinase-3 (GSK-3) inhibitors will end years of speculation on their potential and finally allow the impact of GSK-3 inhibitors to be evaluated clinically. The next few years are likely to be particularly exciting ones for fans of this old enzyme. This review focuses on the role of GSK-3 in the insulin signalling pathway and highlights the evidence implicating the enzyme in insulin resistance. Pharmacological in vitro and in vivo proof-of-concept studies are also discussed, which establish the therapeutic potential of GSK-3 inhibitors as agents for the treatment of Type 2 diabetes.
Frame
Sheelagh
S
Cyclacel Ltd., James Lindsay Place, Dundee, DD1 5JJ, UK. sframe@cyclacel.com
Zheleva
Daniella
D
D000595:Amino Acid Sequence; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D007328:Insulin; D038362:Glycogen Synthase Kinase 3