Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model

• Published in: Cellular and molecular life sciences : CMLS Vol. 67; no. 21; pp. 3711 - 3723
• Main Authors: Luciani, Paola, Deledda, Cristiana, Benvenuti, Susanna, Cellai, Ilaria, Squecco, Roberta, Monici, Monica, Cialdai, Francesca, Luciani, Giorgia, Danza, Giovanna, Di Stefano, Chiara, Francini, Fabio, Peri, Alessandro
• Format: Journal Article
• Language: English
• Published: Basel Basel : SP Birkhäuser Verlag Basel 01.11.2010; SP Birkhäuser Verlag Basel; Springer Nature B.V
• Subjects: Actin Depolymerizing Factors - metabolism; Actins - ultrastructure; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Line; Cellular biology; Cytoskeleton - ultrastructure; Diabetes; diabetic neuropathy; Exenatide; Exendin-4; Gene Expression; Genotype & phenotype; GLP-1; Glucagon-Like Peptide 1 - analogs & derivatives; Glucagon-Like Peptide 1 - genetics; Glucagon-Like Peptide 1 - metabolism; Humans; Ion Channels - metabolism; Life Sciences; Membrane Potentials - drug effects; Neuritogenesis; Neurogenesis - drug effects; Neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neuroprotection; Peptides; Peptides - pharmacology; Phosphorylation; Research Article; Tretinoin - pharmacology; Tubulin - ultrastructure; Venoms - pharmacology; Neuroprotection; Diabetic neuropathy; Neuritogenesis; GLP-1; Exendin-4
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-010-0398-3

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.