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

(Downloading may take up to 30 seconds. If the slide opens in your browser, select File -> Save As to save it.)

Click on image to view larger version.

FIG. 2.
FIG. 2.

Reduced cell mass in FAK-deficient β-cells due to decreased proliferation and enhanced susceptibility to apoptosis. A: Insulin-immunostained pancreatic sections revealed a significant reduction in β-cell area per pancreatic area in RIPcre+fakfl/fl mice (■) compared with RIPcre+fak+/+ littermates (□); n = 5 per genotype. Scale bars, 200 μm. B: β-Cell mass was reduced in RIPcre+fakfl/fl mice (■) compared with RIPcre+fak+/+ littermates (□); n = 3–5 per genotype. C: Pancreatic islet circled by dashed line and Ki67-positive cells pointed by black arrow. RIPcre+fakfl/fl islets (■) show a decreased percentage of Ki67-positive cells per islet compared with RIPcre+fak+/+ littermates (□; original magnification ×40); n = ∼3,000 β-cells per animal from six 4–8-week-old mice per genotype were counted. D: Caspase 3 (Casp3) activation, as assessed by caspase 3 cleavage. Western blot of protein lysates of islets isolated from 4–8-week-old mice showing increased expression of activated caspase 3 in RIPcre+fakfl/fl (■) compared with RIPcre+fak+/+ islets (□); n = 3 per genotype. E: RIPcre+fakfl/fl mice (♦) were more susceptible to hyperglycemia than RIPcre+fak+/+ littermates (◇) after 2 days, but diminished at 14 days postinjection of multiple low doses of STZ, as shown by random blood glucose levels; n = 3–4 per genotype. F: Increased β-cell apoptosis in RIPcre+fakfl/fl mice (■) compared with RIPcre+fak+/+ littermates (□) in basal state or after 2 days of injection of multiple low doses of STZ as assessed by TUNEL (original magnification ×40); n = ∼1,000 β-cells per animal were counted from three to five 6–8-week-old male mice per genotype. *P < 0.05; **P < 0.01; ***P < 0.001. Results represent mean ± SE. +,+/+, RIPcre+fak+/+; +,−/−, RIPcre+fakfl/fl. wks, weeks. Scale bars, 40 μm. (A high-quality digital representation of this figure is available in the online issue.)

This Article

  1. Diabetes vol. 61 no. 7 1708-1718