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1.
Growth Factors ; 34(5-6): 159-165, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27681688

RESUMO

OBJECTIVE: To investigate the role of intrauterine malnourishment in the development and function of pancreatic islet ß-cells. METHODS: Whole-cell patch clamping was used to record voltage-gated calcium channel (VGCC)-mediated currents. Insulin secretion was detected by measuring capacitance using a sequence of sine wave stimuli. VGCC currents and insulin secretion were measured in the small for gestational age (SGA) group treated with human recombinant growth hormone (hGH). RESULTS: The membrane capacitance in the SGA group (6.4 ± 0.9 fF/Pf) was significantly reduced. Calcium current density and peak current density in the SGA group were also markedly decreased, whereas other measurements of calcium channels were unaltered. Treatment with hGH significantly rescued the membrane capacitance, whereas calcium channels were not affected. CONCLUSION: Our data suggest that decreased ß-cell secretion is caused by a decreased expression of calcium channels and reduced calcium currents. hGH restores ß-cell secretion in SGA animals, possibly independently of VGCC.


Assuntos
Canais de Cálcio/metabolismo , Retardo do Crescimento Fetal/metabolismo , Células Secretoras de Insulina/metabolismo , Potenciais de Ação , Animais , Células Cultivadas , Feminino , Hormônio do Crescimento/farmacologia , Humanos , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/fisiologia , Ratos , Ratos Sprague-Dawley
2.
J Membr Biol ; 246(2): 101-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23296347

RESUMO

Pancreatic beta cells act as glucose sensors, in which intracellular ATP ([ATP](i)) are altered with glucose concentration change. The characterization of voltage-gated sodium channels under different [ATP](i) remains unclear. Here, we demonstrated that increasing [ATP](i) within a certain range of concentrations (2-8 mM) significantly enhanced the voltage-gated sodium channel currents, compared with 2 mM cytosolic ATP. This enhancement was attenuated by even high intracellular ATP (12 mM). Furthermore, elevated ATP modulated the sodium channel kinetics in a dose-dependent manner. Increased [ATP](i) shifted both the current-voltage curve and the voltage-dependent inactivation curve of sodium channel to the right. Finally, the sodium channel recovery from inactivation was significantly faster when the intracellular ATP level was increased, especially in 8 mM [ATP](i), which is an attainable concentration by the high glucose stimulation. In summary, our data suggested that elevated cytosolic ATP enhanced the activity of Na(+) channels, which may play essential roles in modulating ß cell excitability and insulin release when blood glucose concentration increases.


Assuntos
Trifosfato de Adenosina/metabolismo , Células Secretoras de Insulina/metabolismo , Animais , Glicemia/metabolismo , Eletrofisiologia , Humanos , Técnicas In Vitro , Cinética , Masculino , Camundongos , Pâncreas/metabolismo
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