| First Author | Jevon D | Year | 2022 |
| Journal | Elife | Volume | 11 |
| PubMed ID | 35559734 | Mgi Jnum | J:328647 |
| Mgi Id | MGI:7283685 | Doi | 10.7554/eLife.76262 |
| Citation | Jevon D, et al. (2022) Local activation of focal adhesion kinase orchestrates the positioning of presynaptic scaffold proteins and Ca(2+) signalling to control glucose-dependent insulin secretion. Elife 11:e76262 |
| abstractText | A developing understanding suggests that spatial compartmentalisation in pancreatic beta cells is critical in controlling insulin secretion. To investigate the mechanisms, we have developed live-cell subcellular imaging methods using the mouse organotypic pancreatic slice. We demonstrate that the organotypic pancreatic slice, when compared with isolated islets, preserves intact beta-cell structure, and enhances glucose-dependent Ca(2+) responses and insulin secretion. Using the slice technique, we have discovered the essential role of local activation of integrins and the downstream component, focal adhesion kinase (FAK), in regulating beta cells. Integrins and FAK are exclusively activated at the beta-cell capillary interface and using in situ and in vitro models we show their activation both positions presynaptic scaffold proteins, like ELKS and liprin, and regulates glucose-dependent Ca(2+) responses and insulin secretion. We conclude that FAK orchestrates the final steps of glucose-dependent insulin secretion within the restricted domain where beta-cell contact the islet capillaries. |
