A critical role of the mechanosensor PIEZO1 in glucose-induced insulin secretion in pancreatic β-cells

Yingying Ye, Mohammad Barghouth, Haiqiang Dou, Cheng Luan, Yongzhi Wang, Alexandros Karagiannopoulos, Xiaoping Jiang, Ulrika Krus, Malin Fex, Quan Zhang, Lena Eliasson, Patrik Rorsman, Enming Zhang, Erik Renström

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review


Glucose-induced insulin secretion depends on β-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 β-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 β-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 β-cell) under experimental conditions emulating T2D (high glucose culture). β-cell-specific Piezo1-knockout mice show impaired glucose tolerance in vivo and reduced glucose-induced insulin secretion, β-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.

TidskriftNature Communications
StatusPublished - 2022 dec.

Ämnesklassifikation (UKÄ)

  • Cell- och molekylärbiologi


Utforska forskningsämnen för ”A critical role of the mechanosensor PIEZO1 in glucose-induced insulin secretion in pancreatic β-cells”. Tillsammans bildar de ett unikt fingeravtryck.

Citera det här