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

American Journal of Physiology. Endocrinology and Metabolism
Yi Wang, Xinfu Guan

Abstract

Glucagon-like peptide-2 (GLP-2) is a neuropeptide secreted from endocrine cells in the gut and neurons in the brain. GLP-2 stimulates intestinal crypt cell proliferation and mucosal blood flow while decreasing gastric emptying and gut motility. However, a GLP-2-mediated signaling network has not been fully established in primary cells. Since the GLP-2 receptor mRNA and protein were highly expressed in the mouse hippocampus, we further characterized that human (125)I-labeled GLP-2(1-33) specifically bound to cultured hippocampal neurons with K(d) = 0.48 nM, and GLP-2 acutely induced subcellular translocalization of the early gene c-Fos. Using the whole cell patch clamp, we recorded barium currents (I(Ba)) flowing through voltage-gated Ca(2+) channels (VGCC) in those neurons in the presence of GLP-2 with and without inhibitors. We showed that GLP-2 (20 nM) enhanced the whole cell I(Ba) mediated by L-type VGCC that was defined using an L-type Ca(2+) channel blocker (nifedipine, 10 microM). Moreover, GLP-2-potentiation of L-type VGCC was abolished in neurons pretreated with a PKA inhibitor (PKI(14-22), 1 microM). Finally, using a fluorescent nonmetabolized glucose analog (6-NBDG) tracing imaging, we showed that glucose was taken up...Continue Reading

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Citations

Jul 26, 2012·American Journal of Physiology. Endocrinology and Metabolism·Xinfu GuanLawrence Chan
Dec 24, 2010·American Journal of Physiology. Endocrinology and Metabolism·Xuemei ShiXinfu Guan
Sep 15, 2014·Regulatory Peptides·Sara Baldassano, Antonella Amato
Jan 22, 2013·Behavioural Brain Research·Takashi IwaiJun-Ichiro Oka
Aug 20, 2010·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·D L SigaletK A Sharkey
Jul 6, 2014·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Xinfu Guan
Jun 14, 2020·International Journal of Molecular Sciences·Mary Jasmin AngChangjong Moon
May 12, 2017·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·B Chen, N Hu

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