Glucagon-like peptide-1 increases beta-cell glucose competence and proliferation by translational induction of insulin-like growth factor-1 receptor expression
- PMID: 20145256
- PMCID: PMC2856261
- DOI: 10.1074/jbc.M109.091116
Glucagon-like peptide-1 increases beta-cell glucose competence and proliferation by translational induction of insulin-like growth factor-1 receptor expression
Abstract
Glucagon-like peptide-1 (GLP-1) protects beta-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 beta-cell proliferation was suppressed by Igf-1r gene inactivation and by IGF-2 immunoneutralization or knockdown. Together our data show that regulation of beta-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.
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References
-
- Egan J. M., Bulotta A., Hui H., Perfetti R. (2003) Diabetes Metab. Res. Rev. 19, 115–123 - PubMed
-
- Drucker D. J. (2006) Cell Metab. 3, 153–165 - PubMed
-
- Gomez E., Pritchard C., Herbert T. P. (2002) J. Biol. Chem. 277, 48146–48151 - PubMed
-
- Arnette D., Gibson T. B., Lawrence M. C., January B., Khoo S., McGlynn K., Vanderbilt C. A., Cobb M. H. (2003) J. Biol. Chem. 278, 32517–32525 - PubMed
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