Emerging targets for diabetes

Abstract

The worldwide epidemic of type 2 diabetes (NIDDM) has been stimulating the search for new concepts and targets for the treatment of this incurable disease. Most current therapies were developed in the absence of defined molecular targets. Increasing knowledge on the biochemical and cellular alterations occurring in NIDDM has led to the development of novel and potentially more effective therapeutic approaches to treat the disease. The role of peroxisome proliferator activated receptors (PPARs) in the regulation of lipid metabolism, insulin and triglycerides leads to the rational design of several PPAR agonists. However, many promising molecules, especially the dual-acting PPARγ/α, are yet to be approved due to safety issues. Meanwhile, two targets, protein tyrosine phosphatase 1B (PTP-1B) and glycogen synthase kinase-3 (GSK-3), have emerged as validated targets for treating this disease. The activity of various non-peptidic small molecules as well as small peptides like PTP-1B inhibitors has been studied. Likewise, GSK-3, which plays a key role in the insulin signalling pathway, has been intensely studied by various companies as a potential target for the development of antidiabetic therapies. This review focuses on PTP-1B and GSK-3 inhibitors studied until now.