Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model.
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.
Luciani
Paola
P
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.
Deledda
Cristiana
C
Benvenuti
Susanna
S
Cellai
Ilaria
I
Squecco
Roberta
R
Monici
Monica
M
Cialdai
Francesca
F
Luciani
Giorgia
G
Danza
Giovanna
G
Di Stefano
Chiara
C
Francini
Fabio
F
Peri
Alessandro
A
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*
D051339:Actin Depolymerizing Factors; D000199:Actins; D007473:Ion Channels; D010455:Peptides; D014404:Tubulin; D014688:Venoms; D014212:Tretinoin; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide