Glucagon-like peptide-2 stimulates the proliferation of cultured rat astrocytes

Glucagon-like peptide-2 (GLP-2) is a potent intestinotrophic/satiety hormone that acts through a G protein-coupled receptor. To determine whether or not GLP-2 has any effect on cellular proliferation on neural cells, we examined the effects of this peptide on cultured astrocytes from rat cerebral cortex. The expression of the GLP-2 receptor gene in both cerebral cortex and astrocytes was determined by RT-PCR and Southern blotting. Also, cells responded to GLP-2, producing cAMP in a dose-dependent manner (EC50 = 0.86 nm). GLP-2 also stimulated the DNA synthesis rate in rat astrocytes. When proliferation was assessed by measuring [3H]thymidine incorporation into DNA or staining cells with crystal violet, GLP-2 produced a dose-dependent increase in both parameters. Similarly, when the numbers of cells in different phases of the cell cycle were measured by flow cytometry, a dose-dependent decrease in those in the G0-G1 phase and an increase in those in the S and G2-M phases were observed after 24 h incubation with GLP-2. By contrast, the number of hypodiploid cells was not affected during the experimental time. Also, GLP-2 produced a significant increase in the mRNAs of c-fos and c-jun when gene expression was determined by Northern blotting. These results suggest that GLP-2 directly stimulates the proliferation of rat astrocytes; this may open new insights in the physiological role of this novel neuropeptide.