Celebrities in the heart, strangers in the pancreatic beta cell: Voltage‐gated potassium channels K_v7.1 and K_v11.1 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

Hormones—Modulators of metabolism

“…These hormones are produced by the Islets of Langerhans in the pancreas. 2 Insulin has anabolic properties and increases the uptake of carbon sources in muscle and adipose tissues and stores them for possible energetic needs. 3 The biological actions of insulin are mediated by insulin receptors A (IR-A) and B (IR-B), which are derived from alternative splicing of exon 11 of the human insulin receptor gene.…”

“…1 The release of insulin and glucagon is fine-tuned by several mechanisms, like neural innervation, a variety of humoral factors (incretin hormones, amino acids, metabolites), cell-cell communication within the islet cells and electrical communication between the cell types. 2 A disturbance of the balance can lead to disorders like Type 2 diabetes mellitus (T2D). 1 To understand the regulating mechanisms of glucose homeostasis the insulin: glucagon ratio (IGR) is a powerful tool to measure the metabolic state.…”

“…Insulin and glucagon are the main hormonal effectors, which are involved in the regulation of blood glucose homeostasis. These hormones are produced by the Islets of Langerhans in the pancreas 2 . Insulin has anabolic properties and increases the uptake of carbon sources in muscle and adipose tissues and stores them for possible energetic needs 3 .…”

“…It is essential that the activities of insulin and glucagon are in balance 1 . The release of insulin and glucagon is fine‐tuned by several mechanisms, like neural innervation, a variety of humoral factors (incretin hormones, amino acids, metabolites), cell–cell communication within the islet cells and electrical communication between the cell types 2 . A disturbance of the balance can lead to disorders like Type 2 diabetes mellitus (T2D) 1 .…”

A randomized, double‐blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women

“…The voltage-gated potassium channel K v 11.1 plays a crucial role in the repolarization phase in the heart 1,2 and is expressed in a range of electrically excitable cells important for glucose homeostasis, such as pancreatic αand β-cells, [3][4][5] intestinal L-cells 6 and skeletal muscle cells. 7 Various pharmaceuticals have the off-target effect of blocking K v 11.1 channels, e.g.…”