References of "Herchuelz, A"
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See detailHeterozygous inactivation of the Na/Ca exchanger increases glucose-induced insulin release, β-cell proliferation, and mass.
Nguidjoe, E.; Sokolow, S.; Bigabwa, S. et al

in Diabetes (2011), 60

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 ... [more ▼]

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. [less ▲]

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See detailNeuronal injury in NCX3 knockout mice following permanent focal cerebral ischemia and in NCX3 knockout cortical neuronal cultures following oxygen-glucose deprivation and glutamate exposure
Cross, J. L.; Meloni, B. P.; Bakker, A. J. et al

in Journal of Experimental Stroke & Translational Medicine (2009), 2(1), 3-9

In this study we subjected NCX3 knockout and wildtype mice to permanent focal cerebral ischemia by intraluminal middle cerebral artery occlusion. Analysis of brain sections by 2,3,5-Triphenyl-2H ... [more ▼]

In this study we subjected NCX3 knockout and wildtype mice to permanent focal cerebral ischemia by intraluminal middle cerebral artery occlusion. Analysis of brain sections by 2,3,5-Triphenyl-2H-tetrazolium chloride staining, 12 hours after middle cerebral artery occlusion revealed no difference in infarct volume between NCX3 knockout and wildtype mice. In addition, we evaluated the effect of NCX3 protein knockdowri on neuronal viability in primary cortical neuronal cultures following in vitro ischemia (oxygen-glucose deprivation) and L-glutamate (glutamate) exposure. In vitro experiments revealed that neuronal viability was higher in NCX3 knockout neuronal cultures than in the wildtype cultures following ischemic and glutamate insults. The reduced sensitivity of neurons from NCX3 knockout mice to in vitro ischemia and excitotoxicity indicates that NCX3 calcium entry mode activity contributes to calcium overload and neuronal death. However our in vivo finding of e lack of differential sensitivity on infarct volume in NCX3 knockout and wildtype mice suggests that any benefit of reduced NCX3 activity is overridden following permanent focal cerebral ischemia. Taken together, these f]ndings suggest that reduced NXC3 activity limits calcium neurotoxicity during severe transient, but not during severe sustained ischemic insults. These results have important implications for the development of the NCX3 protein as a therapeutic target to reduce ischemic brain injury [less ▲]

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See detailTargeted disruption of Na+/Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage
Molinaro, P.; Cuomo, O.; Pignataro, G. et al

in Journal of Neuroscience (2008), 28

Na+/Ca+ exchanger 3 (NCX3), one of the three isoforms of the NCX family, is highly expressed in the brain and is involved in the maintenance of intracellular Na+ and Ca2+ homeostasis. Interestingly ... [more ▼]

Na+/Ca+ exchanger 3 (NCX3), one of the three isoforms of the NCX family, is highly expressed in the brain and is involved in the maintenance of intracellular Na+ and Ca2+ homeostasis. Interestingly, whereas the function of NCX3 under physiological conditions has been determined, its role under anoxia is still unknown. To assess NCX3 role in cerebral ischemia, we exposed ncx3-/- mice to transient middle cerebral artery occlusion followed by reperfusion. In addition, to evaluate the effect of ncx3 ablation on neuronal survival, organotypic hippocampal cultures and primary cortical neurons from ncx3-/- mice were subjected to oxygen glucose deprivation (OGD) plus reoxygenation. Here we report that ncx3 gene suppression leads to a worsening of brain damage after focal ischemia and to a massive neuronal death in all the hippocampal fields of organotypic cultures as well as in cortical neurons from ncx3-/- mice exposed to OGD plus reoxygenation. In addition, in ncx3-/- cortical neurons exposed to hypoxia, NCX currents, recorded in the reverse mode of operation, were significantly lower than those detected in ncx3+/+. From these results, NCX3 protein emerges as a new molecular target that may have a potential therapeutic value in modulating cerebral ischemia [less ▲]

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See detailImpaired neuromuscular transmission and skeletal muscle fiber necrosis in mice lacking Na/Ca exchanger 3
Sokolow, S.; Manto, M.; Gailly, P. et al

in Journal of Clinical Investigation (2004), 113

We produced and analyzed mice deficient for Na/Ca exchanger 3 (NCX3), a protein that mediates cellular Ca(2+) efflux (forward mode) or Ca(2+) influx (reverse mode) and thus controls intracellular Ca(2 ... [more ▼]

We produced and analyzed mice deficient for Na/Ca exchanger 3 (NCX3), a protein that mediates cellular Ca(2+) efflux (forward mode) or Ca(2+) influx (reverse mode) and thus controls intracellular Ca(2+) concentration. NCX3-deficient mice (Ncx3(-/-)) present a skeletal muscle fiber necrosis and a defective neuromuscular transmission, reflecting the absence of NCX3 in the sarcolemma of the muscle fibers and at the neuromuscular junction. The defective neuromuscular transmission is characterized by the presence of electromyographic abnormalities, including low compound muscle action potential amplitude, a decremental response at low-frequency nerve stimulation, an incremental response, and a prominent postexercise facilitation at high-frequency nerve stimulation, as well as neuromuscular blocks. The analysis of quantal transmitter release in Ncx3(-/-) neuromuscular junctions revealed an important facilitation superimposed on the depression of synaptic responses and an elevated delayed release during high-frequency nerve stimulation. It is suggested that Ca(2+) entering nerve terminals is cleared relatively slowly in the absence of NCX3, thereby enhancing residual Ca(2+) and evoked and delayed quantal transmitter release during repetitive nerve stimulation. Our findings indicate that NCX3 plays an important role in vivo in the control of Ca(2+) concentrations in the skeletal muscle fibers and at the neuromuscular junction [less ▲]

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See detailNovel inhibitors of the sodium-calcium exchanger: benzene ring analogues of N-guanidino substituted amiloride derivatives
Rogister, F.; Laeckmann, D.; Plasman, P.-O. et al

in European Journal of Medicinal Chemistry (2001), 36

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See detailVerapamil: an inhibitor of ATP-sensitive K+ channels?
Lebrun, P.; Antoine, M. H.; Ouedraogo, R. et al

Poster (1997, April)

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See detailPyridothiadiazines as potent inhibitors of glucose-induced insulin release
Lebrun, P.; Antoine, M.-H.; Ouedraogo, R. et al

in Physiology and Pathophysiology of the Islets of Langerhans (1997)

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See detailVerapamil, a phenylalkylamine Ca2+ channel blocker, inhibits ATP-sensitive K+ channels in insulin-secreting cells
Lebrun, P.; Antoine, M.-H.; Ouedraogo, R. et al

in Diabetologia (1997), 40

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See detailVerapamil inhibits ATP-sensitive K+ channel in pancreatic B-cells
Ouedraogo, R.; Pirotte, Bernard ULg; Cosgrove, K. E. et al

Conference (1996, December 07)

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See detailActivation of ATP-dependant K+ channels and inhibition of insulin release: effect of BPDZ 62
Lebrun, P.; Antoine, M.-H.; Ouedraogo, R. et al

in Journal of Pharmacology and Experimental Therapeutics (The) (1996), 277

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See detailATP-sensitive K+ channels and insulin release: effect of BPDZ 62
Lebrun, P.; Antoine, M. H.; Ouedraogo, R. et al

Poster (1995, September)

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See detailATP-sensitive K+ channels and insulin release: effect of BPDZ 62
Lebrun, P.; Antoine, M.-H.; Ouedraogo, R. et al

in Diabetologia (1995), 38

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See detailPyridothiadiazines inhibit glucose-induced insulin release by activating ATP-sensitive K+ channels
Lebrun, P.; Antoine, M. H.; Ouedraogo, R. et al

Conference (1994, December 10)

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See detailPyridothiadiazines as potent activators of KATP channels and inhibitors of insulin secretion
Lebrun, Ph.; De Tullio, Pascal ULg; Antoine, M. H. et al

Poster (1994, October)

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See detailCationic and secretory effects of BPDZ 44 and diazoxide in rat pancreatic islets
Antoine, M.-H.; Pirotte, Bernard ULg; Hermann, M. et al

in Experientia (1994), 50

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See detailA pyridothiadiazine (BPDZ 44) as a new and potent activator of ATP-sensitive K+-channels
Pirotte, Bernard ULg; Antoine, M.-H.; De Tullio, Pascal ULg et al

in Biochemical Pharmacology (1994), 47

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See detailA new and potent activator of ATP-sensitive K+ channels
Antoine, M. H.; Pirotte, Bernard ULg; De Tullio, Pascal ULg et al

Poster (1993, November 20)

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See detailBPDZ 44 : a new and potent activator of ATP-sensitive K+ channels
Lebrun, P.; Pirotte, Bernard ULg; Antoine, M. H. et al

Poster (1993, September)

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See detailBPDZ 44: a new and potent activator of ATP-sensitive K+ channels
Lebrun, P.; Pirotte, Bernard ULg; Antoine, M.-H. et al

in Diabetologia (1993), 36

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