Challenges and opportunities with glycogen synthase kinase-3 inhibitors for insulin resistance and Type 2 diabetes treatment

Expert Opin Investig Drugs. 2003 Sep;12(9):1511-9. doi: 10.1517/13543784.12.9.1511.


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.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Design
  • Enzyme Inhibitors / therapeutic use*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Humans
  • Insulin Resistance*


  • Enzyme Inhibitors
  • Glycogen Synthase Kinase 3