Celebrities in the heart, strangers in the pancreatic beta cell: Voltage-gated potassium channels K_v 7.1 and K_v 11.1 bridge long QT syndrome with hyperinsulinaemia as well as type 2 diabetes.

ABSTRACT: Voltage-gated potassium (K_v ) channels play an important role in the repolarization of a variety of excitable tissues, including in the cardiomyocyte and the pancreatic beta cell. Recently, individuals carrying loss-of-function (LoF) mutations in KCNQ1, encoding K_v 7.1, and KCNH2 (hERG), encoding K_v 11.1, were found to exhibit post-prandial hyperinsulinaemia and episodes of hypoglycaemia. These LoF mutations also cause the cardiac disorder long QT syndrome (LQTS), which can be aggravated by hypoglycaemia. Interestingly, patients with LQTS also have a higher burden of diabetes compared to the background population, an apparent paradox in relation to the hyperinsulinaemic phenotype, and KCNQ1 has been identified as a type 2 diabetes risk gene. This review article summarizes the involvement of delayed rectifier K⁺ channels in pancreatic beta cell function, with emphasis on K_v 7.1 and K_v 11.1, using the cardiomyocyte for context. The functional and clinical consequences of LoF mutations and polymorphisms in these channels on blood glucose homeostasis are explored using evidence from pre-clinical, clinical and genome-wide association studies, thereby evaluating the link between LQTS, hyperinsulinaemia and type 2 diabetes.

SUBMITTER: Lubberding AF 

PROVIDER: S-EPMC9286829 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature