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  • Title: GPR119 agonists: a promising new approach for the treatment of type 2 diabetes and related metabolic disorders.
    Author: Shah U.
    Journal: Curr Opin Drug Discov Devel; 2009 Jul; 12(4):519-32. PubMed ID: 19562648.
    Abstract:
    Type 2 diabetes (T2D) and associated obesity have reached epidemic proportions, and there is an increasing need for orally effective agents that regulate glucose homeostasis with a concurrent reduction in body weight. GPR119, a class-A (rhodopsin-like) G protein-coupled receptor, expressed primarily in the human pancreas and gastrointestinal tract, has attracted considerable interest as a T2D drug target in the last three to five years. The activation of GPR119 increases the intracellular accumulation of cAMP, leading to enhanced glucose-dependent insulin secretion and increased levels of the incretin hormones GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic peptide). In rodent models, orally available GPR119-specific agonists have been shown to attenuate blood glucose levels with a simultaneous body weight loss. This review summarizes the research leading to the identification of GPR119 as a potential drug target for T2D and related metabolic disorders. In addition, an overview of the recent progress made in the discovery of orally active GPR119 agonists is provided.
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