Effect of KCNH6 on Hepatic Endoplasmic Reticulum Stress and Glucose Metabolism
Horm Metab Res DOI: 10.1055/a-1177-6814Adult 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 YorkArticle in Thieme eJournals: Table of contents | Abstract | Full text
Source: Hormone and Metabolic Research - Category: Endocrinology Authors: Lu, Jing Shen, Han Li, Qi Xiong, Feng-Ran Yuan, Ming-Xia Yang, Jin-Kui Tags: Endocrine Research Source Type: research