In Vivo Role of Focal Adhesion Kinase in Regulating Pancreatic β-Cell Mass and Function Through Insulin Signaling, Actin Dynamics, and Granule Trafficking

  1. Minna Woo1,2,4,6
  1. 1Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
  2. 2Toronto General Research Institute, Toronto, Ontario, Canada
  3. 3Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
  4. 4Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  5. 5Department of Physiology, University of Toronto, Toronto, Ontario, Canada
  6. 6Department of Medicine, St. Michael’s Hospital, Toronto, Ontario, Canada
  1. Corresponding author: Minna Woo, mwoo{at}, or Patrick E. MacDonald, pmacdonald{at}
  1. E.P.C. and M.C. contributed equally to this study.


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 β-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 β-cells. These RIPcre+fakfl/fl mice exhibited glucose intolerance without changes in insulin sensitivity. Reduced β-cell viability and proliferation resulting in decreased β-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 β-cells exhibited impaired insulin secretion with normal glucose sensing and preserved Ca2+ 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 β-cell viability and function through regulation in insulin signaling, actin dynamics, and granule trafficking.

  • Received September 25, 2011.
  • Accepted February 24, 2012.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

| Table of Contents

This Article

  1. Diabetes vol. 61 no. 7 1708-1718
  1. All Versions of this Article:
    1. db11-1344v1
    2. 61/7/1708 most recent