| Title: |
Patients with Long-QT Syndrome Caused by Impaired hERG -Encoded Kv11.1 Potassium Channel Have Exaggerated Endocrine Pancreatic and Incretin Function Associated with Reactive Hypoglycemia |
| Authors: |
Hyltén-Cavallius, Louise; Iepsen, Eva W.; Wewer Albrechtsen, Nicolai J.; Svendstrup, Mathilde; Lubberding, Anniek F.; Hartmann, Bolette; Jespersen, Thomas; Linneberg, Allan; Christiansen, Michael; Vestergaard, Henrik; Pedersen, Oluf; Holst, Jens J.; Kanters, Jørgen K.; Hansen, Torben; Torekov, Signe S. |
| Source: |
Hyltén-Cavallius, L, Iepsen, E W, Wewer Albrechtsen, N J, Svendstrup, M, Lubberding, A F, Hartmann, B, Jespersen, T, Linneberg, A, Christiansen, M, Vestergaard, H, Pedersen, O, Holst, J J, Kanters, J K, Hansen, T & Torekov, S S 2017, 'Patients with Long-QT Syndrome Caused by Impaired hERG -Encoded Kv11.1 Potassium Channel Have Exaggerated Endocrine Pancreatic and Incretin Function Associated with Reactive Hypoglycemia', Circulation, vol. 135, no. 18, pp. 1705-1719. https://doi.org/10.1161/CIRCULATIONAHA.116.024279 |
| Publication Year: |
2017 |
| Collection: |
University of Southern Denmark: Research Output / Syddansk Universitet |
| Subject Terms: |
arrhythmias; cardiac; glucagon; glucagon-like peptide 1 (GLP-1); glucose; hyperglycemia; hypoglycemia; insulin-secreting cells; long-QT syndrome; potassium channels; voltage-gated; Heart Conduction System/metabolism; Rats; Wistar; Humans; Middle Aged; Insulin/blood; ERG1 Potassium Channel/antagonists & inhibitors; Male; Islets of Langerhans/metabolism; Incretins/metabolism; Case-Control Studies; Action Potentials; Long QT Syndrome/blood; Transfection; RNA Interference; Time Factors; Electrocardiography; Adult; Biomarkers/blood |
| Description: |
Background: Loss-of-function mutations in hERG (encoding the Kv11.1 voltage-gated potassium channel) cause long-QT syndrome type 2 (LQT2) because of prolonged cardiac repolarization. However, Kv11.1 is also present in pancreatic and β cells and intestinal L and K cells, secreting glucagon, insulin, and the incretins glucagon-like peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide), respectively. These hormones are crucial for glucose regulation, and long-QT syndrome may cause disturbed glucose regulation. We measured secretion of these hormones and cardiac repolarization in response to glucose ingestion in LQT2 patients with functional mutations in hERG and matched healthy participants, testing the hypothesis that LQT2 patients have increased incretin and β-cell function and decreased -cell function, and thus lower glucose levels. Methods: Eleven patients with LQT2 and 22 sex-, age-, and body mass index-matched control participants underwent a 6-hour 75-g oral glucose tolerance test with ECG recording and blood sampling for measurements of glucose, insulin, C-peptide, glucagon, GLP-1, and GIP. Results: In comparison with matched control participants, LQT2 patients had 56% to 78% increased serum insulin, serum C-peptide, plasma GLP-1, and plasma GIP responses (P=0.03-0.001) and decreased plasma glucose levels after glucose ingestion (P=0.02) with more symptoms of hypoglycemia (P=0.04). Sixty-three percent of LQT2 patients developed hypoglycemic plasma glucose levels ( |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
0009-7322; 1524-4539 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/28235848; info:eu-repo/semantics/altIdentifier/pissn/0009-7322; info:eu-repo/semantics/altIdentifier/eissn/1524-4539 |
| DOI: |
10.1161/CIRCULATIONAHA.116.024279 |
| Availability: |
https://portal.findresearcher.sdu.dk/da/publications/ee51b124-0e38-4fee-87a7-91445ec02df5; https://doi.org/10.1161/CIRCULATIONAHA.116.024279; https://findresearcher.sdu.dk/ws/files/135422363/Patients_with_Long_QT_Syndrome_Caused_by_Impaired_hERG_Encoded_Kv11.1_Potassium_Channel_Have_Exaggerated_Endocrine_Pancreatic_and_Incretin_Function_Associated_with_Reactive_Hypoglycemia.pdf |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.3A7B093C |
| Database: |
BASE |