| First Author | Cai EP | Year | 2012 |
| Journal | Diabetes | Volume | 61 |
| Issue | 7 | Pages | 1708-18 |
| PubMed ID | 22498697 | Mgi Jnum | J:203602 |
| Mgi Id | MGI:5527515 | Doi | 10.2337/db11-1344 |
| Citation | Cai EP, et al. (2012) In vivo role of focal adhesion kinase in regulating pancreatic beta-cell mass and function through insulin signaling, actin dynamics, and granule trafficking. Diabetes 61(7):1708-18 |
| abstractText | Focal adhesion kinase (FAK) acts as an adaptor at the focal contacts serving as a junction between the extracellular matrix and actin cytoskeleton. Actin dynamics is known as a determinant step in insulin secretion. Additionally, FAK has been shown to regulate insulin signaling. To investigate the essential physiological role of FAK in pancreatic beta-cells in vivo, we generated a transgenic mouse model using rat insulin promoter (RIP)-driven Cre-loxP recombination system to specifically delete FAK in pancreatic beta-cells. These RIPcre(+)fak(fl/fl) mice exhibited glucose intolerance without changes in insulin sensitivity. Reduced beta-cell viability and proliferation resulting in decreased beta-cell mass was observed in these mice, which was associated with attenuated insulin/Akt (also known as protein kinase B) and extracellular signal-related kinase 1/2 signaling and increased caspase 3 activation. FAK-deficient beta-cells exhibited impaired insulin secretion with normal glucose sensing and preserved Ca(2+) influx in response to glucose, but a reduced number of docked insulin granules and insulin exocytosis were found, which was associated with a decrease in focal proteins, paxillin and talin, and an impairment in actin depolymerization. This study is the first to show in vivo that FAK is critical for pancreatic beta-cell viability and function through regulation in insulin signaling, actin dynamics, and granule trafficking. |
