KCNH6 is essential for insulin secretion by regulating intracellular ER Ca store.

Appropriate Ca concentration in the endoplasmic reticulum (ER), modulating cytosolic Ca signal, serves significant roles in physiological function of pancreatic β cells. To maintaining ER homeostasis, Ca movement across the ER membrane is always accompanied by a simultaneous K flux in the opposite direction. KCNH6 was proven to modulate insulin secretion by controlling plasma membrane action potential duration and intracellular Ca influx.

All-potassium channel CRISPR screening reveals a lysine-specific pathway of insulin secretion.

Objective: Genome-scale CRISPR-Cas9 knockout coupled with single-cell RNA sequencing (scRNA-seq) has been used to identify function-related genes. However, this method may knock out too many genes, leading to low efficiency in finding genes of interest. Insulin secretion is controlled by several electrophysiological events, including fluxes of K depolarization and K repolarization.

KCNH6 Enhanced Hepatic Glucose Metabolism through Mitochondrial Ca Regulation and Oxidative Stress Inhibition.

KCNH6 has been proven to affect glucose metabolism and insulin secretion both in humans and mice. Further study revealed that Kcnh6 knockout (KO) mice showed impaired glucose tolerance. However, the precise function of KCNH6 in the liver remains unknown.

High bicarbonate concentration increases glucose-induced insulin secretion in pancreatic β-cells.

Low serum bicarbonate is closely related to type 2 diabetes mellitus. However, the precise role of bicarbonate on glucose homeostasis and insulin secretion remains unknown. In this study, we investigated the effects of bicarbonate concentration on pancreatic β-cells.

Effect of KCNH6 on Hepatic Endoplasmic Reticulum Stress and Glucose Metabolism.

Adult patients with a dysfunctional ether-a-go-go 2 (hERG2) protein, which is encoded by the gene present with hyperinsulinemia and hyperglycemia. However, the mechanism of in glucose metabolism disorders has not been clearly defined. It has been proposed that sustained endoplasmic reticulum (ER) stress is closely concerned with hepatic insulin resistance and inflammation.