Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/135678
Title: Heterozygous inactivation of the Na/Ca exchanger increases glucose-induced insulin release, b-cell proliferation, and mass
Author: Nguidjoe, Evrard
Sokolow, Sophie
Bigabwa, Serge
Pachera, Nathalie
Allagnat, Florent
Vanderwinden, Jean-Marie
Sener, Abdullah
Manto, Mario
Depreter, Marianne
Mast, Jan
Joanny Ordóñez, Géraldine
Montanya Mias, Eduard
Rahier, Jacques
Cardozo, Alessandra K.
Eizirik, Décio L.
Schurmans, Stéphane
Herchuelz, André
Amico, Eva D.
Keywords: Cèl·lules B
Glucosa
Insulina
Proteïnes de membrana
B cells
Glucose
Insulin
Membrane proteins
Issue Date: 2011
Publisher: American Diabetes Association
Abstract: Objective: we have previously shown that overexpression of the Na-Ca exchanger (NCX1), a protein responsible for Ca2+ extrusion from cells, increases β-cell programmed cell death (apoptosis) and reduces β-cell proliferation. To further characterize the role of NCX1 in β-cells under in vivo conditions, we developed and characterized mice deficient for NCX1. Research design and methods: biologic and morphologic methods (Ca2+ imaging, Ca2+ uptake, glucose metabolism, insulin release, and point counting morphometry) were used to assess β-cell function in vitro. Blood glucose and insulin levels were measured to assess glucose metabolism and insulin sensitivity in vivo. Islets were transplanted under the kidney capsule to assess their performance to revert diabetes in alloxan-diabetic mice. Results: heterozygous inactivation of Ncx1 in mice induced an increase in glucose-induced insulin release, with a major enhancement of its first and second phase. This was paralleled by an increase in β-cell proliferation and mass. The mutation also increased β-cell insulin content, proinsulin immunostaining, glucose-induced Ca2+ uptake, and β-cell resistance to hypoxia. In addition, Ncx1+/− islets showed a two- to four-times higher rate of diabetes cure than Ncx1+/+ islets when transplanted into diabetic animals. Conclusions: downregulation of the Na/Ca exchanger leads to an increase in β-cell function, proliferation, mass, and resistance to physiologic stress, namely to various changes in β-cell function that are opposite to the major abnormalities seen in type 2 diabetes. This provides a unique model for the prevention and treatment of β-cell dysfunction in type 2 diabetes and after islet transplantation.
Note: Reproducció del document publicat a: https://doi.org/10.2337/db10-0924
It is part of: Diabetes, 2011, vol. 60, p. 2076-2085
URI: http://hdl.handle.net/2445/135678
Related resource: https://doi.org/10.2337/db10-0924
ISSN: 0012-1797
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)

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