|Reference : Heterozygous inactivation of the Na/Ca exchanger increases glucose-induced insulin relea...|
|Scientific journals : Article|
|Life sciences : Biochemistry, biophysics & molecular biology|
|Heterozygous inactivation of the Na/Ca exchanger increases glucose-induced insulin release, β-cell proliferation, and mass.|
|Nguidjoe, E. [ > > ]|
|Sokolow, S. [ > > ]|
|Bigabwa, S. [ > > ]|
|Pachera, N. [ > > ]|
|D'Amico, E. [ > > ]|
|Allagnat, F. [ > > ]|
|Vanderwinden, J. M. [ > > ]|
|Sener, A. [ > > ]|
|Manto, M. [ > > ]|
|Depreter, M. [ > > ]|
|Mast, J. [ > > ]|
|Joanny, G. [ > > ]|
|Montanya, E. [ > > ]|
|Rahier, J. [ > > ]|
|Cardoso, A. K. [ > > ]|
|Eizirik, D. L. [ > > ]|
|Schurmans, Stéphane [Université de Liège - ULg > Département de sciences fonctionnelles > Biochimie métabolique vétérinaire >]|
|Herchuelz, A. [ > > ]|
|American Diabetes Association|
|[en] We have previously shown that overexpression of the Na-Ca exchanger (NCX1), a protein responsible for Ca(2+) 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 (Ca(2+) imaging, Ca(2+) 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 Ca(2+) 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.
|Researchers ; Professionals|
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