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.

Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model / P. Luciani;C. Deledda;S. Benvenuti;I. Cellai;R. Squecco;M. Monici;F. Cialdai;G. Luciani;G. Danza;C. D. Stefano;F. Francini;A. Peri. - In: CELLULAR AND MOLECULAR LIFE SCIENCES. - ISSN 1420-9071. - STAMPA. - 67:(2010), pp. 3711-3723. [10.1007/s00018-010-0398-3]

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

BENVENUTI, SUSANNA;SQUECCO, ROBERTA;CIALDAI, FRANCESCA;DANZA, GIOVANNA;PERI, ALESSANDRO
2010

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.
2010
67
3711
3723
P. Luciani;C. Deledda;S. Benvenuti;I. Cellai;R. Squecco;M. Monici;F. Cialdai;G. Luciani;G. Danza;C. D. Stefano;F. Francini;A. Peri
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/396103
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