title: Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model.
abstract: Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptide with neurotrophic properties, as assessed in animal cell models. Exendin-4, a GLP-1 analogue, has been recently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to morphologically, structurally, and functionally characterize the differentiating actions of exendin-4 using a human neuronal cell model (i.e., SH-SY5Y cells). We found that exendin-4 increased the number of neurites paralleled by dramatic changes in intracellular actin and tubulin distribution. Electrophysiological analyses showed an increase in cell membrane surface and in stretch-activated-channels sensitivity, an increased conductance of Na(+) channels and amplitude of Ca(++) currents (T- and L-type), typical of a more mature neuronal phenotype. To our knowledge, this is the first demonstration that exendin-4 promotes neuronal differentiation in human cells. Noteworthy, our data support the claimed favorable role of exendin-4 against diabetic neuropathy as well as against different neurodegenerative diseases.
authors.affiliation: Department of Clinical Physiopathology, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies (DENOThe), University of Florence, Florence, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Luciani
authors.forename: Cristiana
authors.initials: C
authors.lastname: Deledda
authors.forename: Susanna
authors.initials: S
authors.lastname: Benvenuti
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cellai
authors.forename: Roberta
authors.initials: R
authors.lastname: Squecco
authors.forename: Monica
authors.initials: M
authors.lastname: Monici
authors.forename: Francesca
authors.initials: F
authors.lastname: Cialdai
authors.forename: Giorgia
authors.initials: G
authors.lastname: Luciani
authors.forename: Giovanna
authors.initials: G
authors.lastname: Danza
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Stefano
authors.forename: Fabio
authors.initials: F
authors.lastname: Francini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peri
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000648:ultrastructure; D002460:Cell Line; D003599:Cytoskeleton / Q000648:ultrastructure; D000077270:Exenatide; D015870:Gene Expression; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D014212:Tretinoin / Q000494:pharmacology; D014404:Tubulin / Q000648:ultrastructure; D014688:Venoms / Q000494:pharmacology*
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D007473:Ion Channels; D010455:Peptides; D014404:Tubulin; D014688:Venoms; D014212:Tretinoin; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide