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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Cornu, Marion Modi, Honey Kawamori, Dan Kulkarni, Rohit N. Joffraud, Magali Thorens, Bernard |
| Abstract | Glucagon-like peptide-1 (GLP-1) protects β-cells against apoptosis, increases their glucose competence, and induces their proliferation. We previously demonstrated that the anti-apoptotic effect was mediated by an increase in insulin-like growth factor-1 receptor (IGF-1R) expression and signaling, which was dependent on autocrine secretion of insulin-like growth factor 2 (IGF-2). Here, we further investigated how GLP-1 induces IGF-1R expression and whether the IGF-2/IGF-1R autocrine loop is also involved in mediating GLP-1-increase in glucose competence and proliferation. We show that GLP-1 up-regulated IGF-1R expression by a protein kinase A-dependent translational control mechanism, whereas isobutylmethylxanthine, which led to higher intracellular accumulation of cAMP than GLP-1, increased both IGF-1R transcription and translation. We then demonstrated, using MIN6 cells and primary islets, that the glucose competence of these cells was dependent on the level of IGF-1R expression and on IGF-2 secretion. We showed that GLP-1-induced primary β-cell proliferation was suppressed by Igf-1r gene inactivation and by IGF-2 immunoneutralization or knockdown. Together our data show that regulation of β-cell number and function by GLP-1 depends on the cAMP/protein kinase A mediated-induction of IGF-1R expression and the increased activity of an IGF-2/IGF-1R autocrine loop. |
| Related Links | http://www.jbc.org/content/285/14/10538.abstract |
| Ending Page | 10545 |
| Starting Page | 10538 |
| Page Count | 8 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 14 |
| Volume Number | 285 |
| DOI | 10.1074/jbc.M109.091116 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2010-04-02 |
| Access Restriction | Open |
| Subject Keyword | Insulin Insulin-like Growth Factor (IGF) Pancreatic Islet Receptors Translation Control GLP-1 Gluco-incretin IGF-1 Receptor Proliferation Secretion Metabolism |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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