Spatiotemporal Correlation Spectroscopy Reveals a Protective Effect of Peptide-Based GLP-1 Receptor Agonism against Lipotoxicity on Insulin Granule Dynamics in Primary Human β-Cells.

GLP-1 receptor agonism fluorescence iMSD insulin secretory granule dynamics pancreatic islets syncollin β-cells

Journal

Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003

Informations de publication

Date de publication:
03 Sep 2021
Historique:
received: 16 07 2021
revised: 18 08 2021
accepted: 02 09 2021
entrez: 28 9 2021
pubmed: 29 9 2021
medline: 29 9 2021
Statut: epublish

Résumé

Glucagon-like peptide-1 receptor (GLP-1R) agonists are being used for the treatment of type 2 diabetes (T2D) and may have beneficial effects on the pancreatic β-cells. Here, we evaluated the effects of GLP-1R agonism on insulin secretory granule (ISG) dynamics in primary β-cells isolated from human islets exposed to palmitate-induced lipotoxic stress. Islets cells were exposed for 48 h to 0.5 mM palmitate (hereafter, 'Palm') with or without the addition of a GLP-1 agonist, namely 10 nM exendin-4 (hereafter, 'Ex-4'). Dissociated cells were first transfected with syncollin-EGFP in order to fluorescently mark the ISGs. Then, by applying a recently established spatiotemporal correlation spectroscopy technique, the average structural (i.e., size) and dynamic (i.e., the local diffusivity and mode of motion) properties of ISGs are extracted from a calculated imaging-derived Mean Square Displacement (

Identifiants

pubmed: 34575477
pii: pharmaceutics13091403
doi: 10.3390/pharmaceutics13091403
pmc: PMC8464798
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : H2020 European Research Council
ID : 866127

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Auteurs

Gianmarco Ferri (G)

Laboratorio NEST-Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy.

Marta Tesi (M)

Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, 56127 Pisa, Italy.

Luca Pesce (L)

Laboratorio NEST-Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy.

Marco Bugliani (M)

Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, 56127 Pisa, Italy.

Francesca Grano (F)

Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, 56127 Pisa, Italy.

Margherita Occhipinti (M)

Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, 56127 Pisa, Italy.

Mara Suleiman (M)

Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, 56127 Pisa, Italy.

Carmela De Luca (C)

Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, 56127 Pisa, Italy.

Lorella Marselli (L)

Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, 56127 Pisa, Italy.

Piero Marchetti (P)

Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, 56127 Pisa, Italy.

Francesco Cardarelli (F)

Laboratorio NEST-Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy.

Classifications MeSH