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.