title: Pharmacogenomics of glinides.
abstract: Glinides, including repaglinide, nateglinide and mitiglinide, are a type of fasting insulin secretagogue that could help to mimic early-phase insulin release, thus providing improved control of the postprandial glucose levels. Glinides stimulate insulin secretion by inhibiting ATP-sensitive potassium channels in the pancreatic β-cell membrane. Although glinides have been widely used clinically and display excellent safety and efficacy, the response to glinides varies among individuals, which is partially due to genetic factors involved in drug absorption, distribution, metabolism and targeting. Several pharmacogenomic studies have demonstrated that variants of genes involved in the pharmacokinetics or pharmacodynamics of glinides are associated with the drug response. Polymorphisms of genes involved in drug metabolism, such as CYP2C9, CYP2C8 and SLCO1B1, may influence the efficacy of glinides and the incidence of adverse effects. In addition, Type 2 diabetes mellitus susceptibility genes, such as KCNQ1, PAX4 and BETA2, also influence the efficacy of glinides. In this article, we review and discuss current pharmacogenomics researches on glinides, and hopefully provide useful data and proof for clinical application.
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology & Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.forename: Cheng
authors.initials: C
authors.lastname: Hu
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
mesh_terms: D002219:Carbamates / Q000378:metabolism / Q000627:therapeutic use; D003510:Cyclohexanes / Q000378:metabolism / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000627:therapeutic use*; D008658:Inactivation, Metabolic / Q000235:genetics*; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D054833:Isoindoles / Q000378:metabolism / Q000627:therapeutic use; D054086:KATP Channels / Q000037:antagonists & inhibitors; D000077715:Nateglinide; D010597:Pharmacogenetics; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D010880:Piperidines / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D002219:Carbamates; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D007328:Insulin; D054833:Isoindoles; D054086:KATP Channels; D010880:Piperidines; D000077715:Nateglinide; D010649:Phenylalanine; C072379:repaglinide; C087255:mitiglinide
keywords: T2DM; glinides; mitiglinide; nateglinide; pharmacogenomics; repaglinide