GLP-2 potentiates L-type Ca²⁺ channel activity associated with stimulated glucose uptake in hippocampal neurons

Abstract

Wang Y, Guan X. GLP-2 potentiates L-type Ca 2ϩ channel activity associated with stimulated glucose uptake in hippocampal neurons.

Glucagon-like peptide-2-stimulated protein synthesis through the PI 3-kinase-dependent Akt-mTOR signaling pathway

“…Neurons were obtained from 1-day-old neonatal mice and cultured as described previously (28). In brief, the hippocampus was dissected in F-12 medium, digested with L15-NeurobasalA medium containing 0.1% trypsin and 0.1% DNAase at 37°C for 30 min, triturated with a sterile pipette tip on ice, and centrifuged at 1,000 rpm at 4°C for 5 min.…”

“…Hippocampal neurons cultured on glass coverslips on day 6 in vitro were exposed to 20 nM GLP-2 for 30 min to localize phosphorylation of Akt and mTOR as described previously (28). In brief, cells on coverslips then were fixed in 4% paraformaldehyde in PBS for 20 min, permeabilized in PBS containing 0.1% Triton X-100, and blocked in 10% normal donkey serum for 1 h. Cells were incubated with primary antibodies [guinea pig PGP9.5, Millipore Intl.…”

“…In addition to HEK 293-transfected cells, we wanted to test whether GLP-2-mediated stimulation of protein synthesis is physiologically relevant in the mouse hippocampal neurons (expressing native GLP-2R) that had been characterized and used in our electrophysiology study (28). Results are shown in Figs.…”

“…However, GLP-2 receptor (GLP-2R) is localized to enteric neurons, enteroendocrine cells, and subepithelial myofibroblasts, but not enterocytes (5,14,22,23,33), suggesting that GLP-2-induced trophic actions on the epithelium are mediated indirectly. Our recent study indicates that GLP-2 directly modulates L-type calcium channel activity in primary neurons (28), which might be attributed to GLP-2-triggered release of neurotransmitters, hormones, or local growth factors from GLP-2R-expressing cells. To fulfill this function, however, de novo synthesis of protein must be initiated and sustained somehow.…”

GLP-2: What do we know? What are we going to discover?

“…By peripheral administration, the neuropeptides label the blood-brain barrier-free area postrema and diffuse into the adjacent regions [35]. GLP-2R is expressed also in key regions of the brain including the hypothalamus and the hippocampus [30,36]. In the hypothalamus the activation of the GLP-2R reduces gastric emptying probably through the melanocortin system [37].…”