Channeling dysglycemia: ion-channel variations perturbing glucose homeostasis

Maintaining blood glucose homeostasis is a complex process that depends on pancreatic islet hormone secretion. Hormone secretion from islets is coupled to calcium entry which results from regenerative islet cell electrical activity. Therefore, the ionic mechanisms that regulate calcium entry into islet cells are crucial for maintaining normal glucose homeostasis. Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs), including five located in or near ion-channel or associated subunit genes, which show an association with human diseases characterized by dysglycemia. This review focuses on polymorphisms and mutations in ion-channel genes that are associated with perturbations in human glucose homeostasis and discusses their potential roles in modulating pancreatic islet hormone secretion.