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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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. / Lubberding, Anniek F.; Juhl, Christian R.; Skovhoj, Emil Z.; Kanters, Jorgen K.; Mandrup-Poulsen, Thomas; Torekov, Signe S.
In: Acta Physiologica, Vol. 234, No. 3, 13781, 2022.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Celebrities in the heart, strangers in the pancreatic beta cell
T2 - Voltage-gated potassium channels Kv7.1 and Kv11.1 bridge long QT syndrome with hyperinsulinaemia as well as type 2 diabetes
AU - Lubberding, Anniek F.
AU - Juhl, Christian R.
AU - Skovhoj, Emil Z.
AU - Kanters, Jorgen K.
AU - Mandrup-Poulsen, Thomas
AU - Torekov, Signe S.
PY - 2022
Y1 - 2022
N2 - 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 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 K(v)7.1 and K(v)11.1, 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.
AB - 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 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 K(v)7.1 and K(v)11.1, 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.
KW - cardiac
KW - delayed rectifier
KW - glucose homeostasis
KW - insulin
KW - KCNH2
KW - KCNQ1
KW - K-v
KW - pancreatic islet
KW - GENOME-WIDE ASSOCIATION
KW - BECKWITH-WIEDEMANN SYNDROME
KW - DEPENDENT K+ CHANNELS
KW - INSULIN-SECRETION
KW - I-KS
KW - ELECTRICAL-ACTIVITY
KW - ACTION-POTENTIALS
KW - MOLECULAR PHYSIOLOGY
KW - GENETIC ARCHITECTURE
KW - SUSCEPTIBILITY LOCI
U2 - 10.1111/apha.13781
DO - 10.1111/apha.13781
M3 - Review
C2 - 34990074
VL - 234
JO - Acta Physiologica
JF - Acta Physiologica
SN - 1748-1708
IS - 3
M1 - 13781
ER -
ID: 291227390