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

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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.

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Acknowledgments

This study was supported by a grant from Ente Cassa di Risparmio di Firenze.

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Authors and Affiliations

  1. Endocrine Unit, 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

    Paola Luciani, Cristiana Deledda, Susanna Benvenuti, Ilaria Cellai, Giovanna Danza, Chiara Di Stefano & Alessandro Peri

  2. Joint Laboratory ASAcampus, ASA Research Division, Department of Clinical Physiopathology, University of Florence, Florence, Italy

    Monica Monici & Francesca Cialdai

  3. Department of Physiological Sciences, University of Florence, Florence, Italy

    Roberta Squecco, Giorgia Luciani & Fabio Francini

  4. Endocrine Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy

    Alessandro Peri

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  1. Paola Luciani
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Luciani, P., Deledda, C., Benvenuti, S. et al. Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model. Cell. Mol. Life Sci. 67, 3711–3723 (2010). https://doi.org/10.1007/s00018-010-0398-3

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