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Celebrities in the heart, strangers in the pancreatic beta cell: Voltage‐gated potassium channels Kv7.1 and Kv11.1 bridge long QT syndrome with hyperinsulinaemia as well as type 2 diabetes
Voltage‐gated potassium (Kv) 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 Kv7.1, and KCNH2 (hERG), encoding Kv11...
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Published in: | Acta Physiologica 2022-03, Vol.234 (3), p.n/a |
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description | Voltage‐gated potassium (Kv) 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 Kv7.1, and KCNH2 (hERG), encoding Kv11.1, 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 Kv7.1 and Kv11.1, 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. |
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Recently, individuals carrying loss‐of‐function (LoF) mutations in KCNQ1, encoding Kv7.1, and KCNH2 (hERG), encoding Kv11.1, 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 Kv7.1 and Kv11.1, 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.</description><identifier>ISSN: 1748-1708</identifier><identifier>EISSN: 1748-1716</identifier><identifier>DOI: 10.1111/apha.13781</identifier><identifier>PMID: 34990074</identifier><language>eng</language><publisher>Stockholm: Wiley Subscription Services, Inc</publisher><subject>Beta cells ; cardiac ; Cardiomyocytes ; delayed rectifier ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Genome-wide association studies ; Genomes ; glucose homeostasis ; Homeostasis ; Hypoglycemia ; insulin ; KCNH2 ; KCNQ1 ; KCNQ1 protein ; Long QT syndrome ; Mutation ; Pancreas ; pancreatic islet ; Phenotypes ; Potassium ; Potassium channels (delayed-rectifying) ; Potassium channels (voltage-gated) ; Review</subject><ispartof>Acta Physiologica, 2022-03, Vol.234 (3), p.n/a</ispartof><rights>2022 The Authors. published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.</rights><rights>2022. 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Recently, individuals carrying loss‐of‐function (LoF) mutations in KCNQ1, encoding Kv7.1, and KCNH2 (hERG), encoding Kv11.1, 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 Kv7.1 and Kv11.1, using the cardiomyocyte for context. 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Recently, individuals carrying loss‐of‐function (LoF) mutations in KCNQ1, encoding Kv7.1, and KCNH2 (hERG), encoding Kv11.1, 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 Kv7.1 and Kv11.1, using the cardiomyocyte for context. 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subjects | Beta cells cardiac Cardiomyocytes delayed rectifier Diabetes Diabetes mellitus (non-insulin dependent) Genome-wide association studies Genomes glucose homeostasis Homeostasis Hypoglycemia insulin KCNH2 KCNQ1 KCNQ1 protein Long QT syndrome Mutation Pancreas pancreatic islet Phenotypes Potassium Potassium channels (delayed-rectifying) Potassium channels (voltage-gated) Review |
title | Celebrities in the heart, strangers in the pancreatic beta cell: Voltage‐gated potassium channels Kv7.1 and Kv11.1 bridge long QT syndrome with hyperinsulinaemia as well as type 2 diabetes |
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