Our research focuses on the voltage-gated K+ channels Kv11.1 (encoded by KCNH2) and Kv7.1 (encoded by KCNQ1), which are expressed in pancreatic ! cells and cardiomyocytes. These channels are well-known to regulate cardiac repolarization and loss-of-function mutations in either KCNH2 and KCNQ1 cause the cardiac disease long QT syndrome (LQT). While Kv7.1 and Kv11.1 have also been implicated in insulin secretion, the underlying mechanisms and their broader metabolic roles remain poorly understood.
We aim to explore the dual roles of Kv7.1 and Kv11.1 in metabolism and cardiac function with the perspective of identifying novel, cardiac-safe type 2 diabetes drug targets. Type 2 diabetes is a growing global health issue and despite recent advances, the heterogeneity of this disease challenges the one-size-fits-all treatment approaches, highlighting the need for new therapeutic strategies and drug targets. Using pharmacological tools, genetic knockdown and animal models, we have uncovered unconventional roles of Kv11.1 and Kv7.1 in pancreatic hormone secretion and glucose metabolism, with distinct mechanisms of action in heart and pancreas.
To translate these findings to the human context, we plan to analyze data from the UK biobank to assess how genetic variation in KCNQ1 and KCNH2 influence cardiac and metabolic health. We will integrate genomic, metabolic and cardiac phenotypic data to determine how the cardiac and pancreatic functions of Kv7.1 and Kv11.1 are linked and co-present, thereby lending valuable insights to the goal of identifying therapeutic targets for type 2 diabetes in the future.
