Dataset Information

CREB mediates the insulinotropic and anti-apoptotic effects of GLP-1 signaling in adult mouse β-cells.

ABSTRACT:

Objective

Glucagon-like peptide-1 (GLP-1) plays a major role in pancreatic β-cell function and survival by increasing cytoplasmic cAMP levels, which are thought to affect transcription through activation of the basic leucine zipper (bZIP) transcription factor CREB. Here, we test CREB function in the adult β-cell through inducible gene deletion.

Methods

We employed cell type-specific and inducible gene ablation to determine CREB function in pancreatic β-cells in mice.

Results

By ablating CREB acutely in mature β-cells in tamoxifen-treated Creb (loxP/loxP);Pdx1-CreERT2 mice, we show that CREB has little impact on β-cell turnover, in contrast to what had been postulated previously. Rather, CREB is required for GLP-1 to elicit its full effects on stimulating glucose-induced insulin secretion and protection from cytokine-induced apoptosis. Mechanistically, we find that CREB regulates expression of the pro-apoptotic gene p21 (Cdkn1a) in β-cells, thus demonstrating that CREB is essential to mediating this critical aspect of GLP-1 receptor signaling.

Conclusions

In sum, our studies using conditional gene deletion put into question current notions about the importance of CREB in regulating β-cell function and mass. However, we reveal an important role for CREB in the β-cell response to GLP-1 receptor signaling, further validating CREB as a therapeutic target for diabetes.

SUBMITTER: Shin S

PROVIDER: S-EPMC4216406 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

CREB mediates the insulinotropic and anti-apoptotic effects of GLP-1 signaling in adult mouse β-cells.

Shin Soona S Le Lay John J Everett Logan J LJ Gupta Rana R Rafiq Kiran K Kaestner Klaus H KH

Molecular metabolism 20140823 8

<h4>Objective</h4>Glucagon-like peptide-1 (GLP-1) plays a major role in pancreatic β-cell function and survival by increasing cytoplasmic cAMP levels, which are thought to affect transcription through activation of the basic leucine zipper (bZIP) transcription factor CREB. Here, we test CREB function in the adult β-cell through inducible gene deletion.<h4>Methods</h4>We employed cell type-specific and inducible gene ablation to determine CREB function in pancreatic β-cells in mice.<h4>Results</h ...[more]

PMID: 25379405

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Dataset Information

CREB mediates the insulinotropic and anti-apoptotic effects of GLP-1 signaling in adult mouse β-cells.

Objective

Methods

Results

Conclusions

Publications

CREB mediates the insulinotropic and anti-apoptotic effects of GLP-1 signaling in adult mouse β-cells.

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