Disruption of Growth Factor Receptor–Binding Protein 10 in the Pancreas Enhances β-Cell Proliferation and Protects Mice From Streptozotocin-Induced β-Cell Apoptosis

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FIG. 4.FIG. 4.FIG. 4.FIG. 4.
FIG. 4.

Pancreatic-specific knockout of Grb10 increased β-cell mass, insulin granule numbers, and insulin/IGF-1 signaling in islets. pGrb10KO mice and WT littermates were fed with 60% HFD for 16 weeks. A: Average β-cell mass between male pGrb10KO (n = 4) and WT littermates (n = 3). B: Insulin granule numbers in islets of male pGrb10KO (n = 4) and WT littermates (n = 3) were detected. The numbers of docked granules were measured in a cell-surface area of 100 μm2. Scale bars, 2 μm. The data represent mean ± SEM. C: The average β-cell size was analyzed from male pGrb10KO and WT littermates (n = 4/group; >500 cells were counted per slide) using Image-Pro Plus software (Version 5.0; Media Cybernetics, Inc). D: Insulin signaling and IGF-1 signaling in β-cell mass. Islets were isolated from HFD-fed male pGrb10KO and WT control mice (n = 5/group), serum starved for 2 h, and treated with insulin (100 nmol/L) or IGF-1 (100 nmol/L) for 30 min. Phosphorylation and the protein levels of Akt Thr308 and ERK1/2 Thr202/Tyr204 were determined by Western blot using specific antibodies as indicated. E: mTOR signaling in β-cell mass. Islets were isolated from male pGrb10KO and WT control mice (n = 5/group), serum starved for 2 h, and treated with insulin (100 nmol/L) with or without wortmannin (100 nmol/L) for 30 min. Phosphorylation and the protein levels of Akt Thr308 and Ser473, ERK1/2 Thr202/Tyr204, p70S6K Thr389, and 4E-BP1 Thr37/46 were determined by Western blot using specific antibodies as indicated. Data were quantified by using the Scion Image program (Scion Corporation, Frederick, MD). Black bars, Grb10 flox+/−; white bars, pGrb10 KO. The data represent mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (t test).

This Article

  1. Diabetes vol. 61 no. 12 3189-3198