Jing Lu, Han Shen, Qi Li, Feng-Ran Xiong, Ming-Xia Yuan, Jin-Kui Yang
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 2020 SepAdult patients with a dysfunctional ether-a-go-go 2 (hERG2) protein, which is encoded by the KCNH6 gene, present with hyperinsulinemia and hyperglycemia. However, the mechanism of KCNH6 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. Here, we demonstrate that Kcnh6 knockout (KO) mice had impaired glucose tolerance and increased levels of hepatic apoptosis, in addition to displaying an increased insulin resistance that was mediated by high ER stress levels. By contrast, overexpression of KCNH6 in primary hepatocytes led to a decrease in ER stress and apoptosis induced by thapsigargin. Similarly, induction of Kcnh6 by tail vein injection into KO mice improved glucose tolerance by reducing ER stress and apoptosis. Furthermore, we show that KCNH6 alleviated hepatic ER stress, apoptosis, and inflammation via the NFκB-IκB kinase (IKK) pathway both in vitro and in vivo. In summary, our study provides new insights into the causes of ER stress and subsequent induction of primary hepatocytes apoptosis. © Georg Thieme Verlag KG Stuttgart · New York.
Jing Lu, Han Shen, Qi Li, Feng-Ran Xiong, Ming-Xia Yuan, Jin-Kui Yang. Effect of KCNH6 on Hepatic Endoplasmic Reticulum Stress and Glucose Metabolism. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2020 Sep;52(9):669-675
PMID: 32750722
View Full Text