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A critical role of the mechanosensor PIEZO1 in glucose-induced insulin secretion in pancreatic ß-cells.
Ye, Yingying; Barghouth, Mohammad; Dou, Haiqiang; Luan, Cheng; Wang, Yongzhi; Karagiannopoulos, Alexandros; Jiang, Xiaoping; Krus, Ulrika; Fex, Malin; Zhang, Quan; Eliasson, Lena; Rorsman, Patrik; Zhang, Enming; Renström, Erik.
Afiliación
  • Ye Y; Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Unit of Islet Pathophysiology, Lund University, 20502, Malmö, Sweden.
  • Barghouth M; Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Unit of Islet Pathophysiology, Lund University, 20502, Malmö, Sweden.
  • Dou H; Metabolic Research Unit, Institute of Neuroscience and Physiology, Department of Physiology, University of Göteborg, 405 30, Göteborg, Sweden.
  • Luan C; Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Unit of Islet Pathophysiology, Lund University, 20502, Malmö, Sweden.
  • Wang Y; Section for Surgery, Department of Clinical Sciences Malmö, Lund University, 20502, Malmö, Sweden.
  • Karagiannopoulos A; Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Unit of Islet Cell Exocytosis, Lund University, 20502, Malmö, Sweden.
  • Jiang X; Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Unit of Islet Pathophysiology, Lund University, 20502, Malmö, Sweden.
  • Krus U; Institution of Physical Science and Technology, Southwest University, Chongqing, 400715, China.
  • Fex M; Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Unit of Islet Pathophysiology, Lund University, 20502, Malmö, Sweden.
  • Zhang Q; Lund University Diabetes Centre, Department of Clinical Sciences in Malmö, Unit of Molecular Metabolism, Malmö University Hospital, Lund University, 20502, Malmö, Sweden.
  • Eliasson L; Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 7LE, UK.
  • Rorsman P; Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Unit of Islet Cell Exocytosis, Lund University, 20502, Malmö, Sweden.
  • Zhang E; Metabolic Research Unit, Institute of Neuroscience and Physiology, Department of Physiology, University of Göteborg, 405 30, Göteborg, Sweden.
  • Renström E; Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 7LE, UK.
Nat Commun ; 13(1): 4237, 2022 07 22.
Article en En | MEDLINE | ID: mdl-35869052
Glucose-induced insulin secretion depends on ß-cell electrical activity. Inhibition of ATP-regulated potassium (KATP) channels is a key event in this process. However, KATP channel closure alone is not sufficient to induce ß-cell electrical activity; activation of a depolarizing membrane current is also required. Here we examine the role of the mechanosensor ion channel PIEZO1 in this process. Yoda1, a specific PIEZO1 agonist, activates a small membrane current and thereby triggers ß-cell electrical activity with resultant stimulation of Ca2+-influx and insulin secretion. Conversely, the PIEZO1 antagonist GsMTx4 reduces glucose-induced Ca2+-signaling, electrical activity and insulin secretion. Yet, PIEZO1 expression is elevated in islets from human donors with type-2 diabetes (T2D) and a rodent T2D model (db/db mouse), in which insulin secretion is reduced. This paradox is resolved by our finding that PIEZO1 translocates from the plasmalemma into the nucleus (where it cannot influence the membrane potential of the ß-cell) under experimental conditions emulating T2D (high glucose culture). ß-cell-specific Piezo1-knockout mice show impaired glucose tolerance in vivo and reduced glucose-induced insulin secretion, ß-cell electrical activity and Ca2+ elevation in vitro. These results implicate mechanotransduction and activation of PIEZO1, via intracellular accumulation of glucose metabolites, as an important physiological regulator of insulin secretion.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 / Glucosa Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 / Glucosa Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido