ABSTRACT
Diabetes mellitus (DM) is a major worldwide health problem and its prevalence has been rapidly increasing in the last century. It is caused by defects in insulin secretion or insulin action or both, leading to hyperglycemia. Of the various types of DM, type 2 occurs most frequently. Multiple genes and their interactions are involved in the insulin secretion pathway. Insulin secretion is mediated through the ATP-sensitive potassium (KATP) channel in pancreatic beta cells. This channel is a heteromeric protein, composed of four inward-rectifier potassium ion channel (Kir6.2) tetramers, which form the pore of the KATP channel, as well as sulfonylurea receptor 1 subunits surrounding the pore. Kir6.2 is encoded by the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene, a member of the potassium channel genes. Numerous studies have reported the involvement of single nucleotide polymorphisms of the KCNJ11 gene and their interactions in the susceptibility to DM. This review discusses the current evidence for the contribution of common KCNJ11 genetic variants to the development of DM. Future studies should concentrate on understanding the exact role played by these risk variants in the development of DM.
Subject(s)
Diabetes Mellitus/genetics , Polymorphism, Genetic , Potassium Channels, Inwardly Rectifying/genetics , Cell Membrane/metabolism , Diabetes Mellitus/pathology , Genetic Predisposition to Disease , Genetic Variation , Genome-Wide Association Study , Humans , Insulin/metabolism , Insulin Secretion , Insulin-Secreting Cells/metabolism , Mutation , Polymorphism, Single Nucleotide , Risk Factors , Sulfonylurea Receptors/metabolismABSTRACT
Diabetes mellitus (DM) is a major health problem worldwide and it will rapidly increase. This disease is characterized by hyperglycemia caused by defects in insulin secretion, insulin action or both. DM has three types: T1DM, T2M and gestational DM (GDM), of them T2DM is more frequent. Multiple genes and their interactions are involved in insulin secretion pathway. Sulfonylurea receptor encoded by ABCC8 gene, together with inward-rectifier potassium ion channel (Kir6.2) regulates insulin secretion by ATP-sensitive K(+) (KATP) channel located in the plasma membranes. Disruption of these molecules by different mutations is responsible for risk of DM. Several single nucleotide polymorphisms (SNPs) of ABCC8 gene and their interaction are involved in pathogenicity of DM. This review summarizes the current evidence of contribution of ABC8 genetic variants to the development of DM.
