RESUMEN

The aim of the present research was to explore the mechanisms underlying the role of dopamine in the regulation of insulin secretion in beta cells. The effect of dopamine on insulin secretion was investigated on INS 832/13 cell line upon glucose and other secretagogues stimulation. Results show that dopamine significantly inhibits insulin secretion stimulated by both glucose and other secretagogues, while it has no effect on the basal secretion. This effect requires the presence of dopamine during incubation with the various secretagogues. Both electron microscopy and immunohistochemistry indicate that in beta cells the D2 dopamine receptor is localized within the insulin granules. Blocking dopamine entry into the insulin granules by inhibiting the VMAT2 transporter with tetrabenazine causes a significant increase in ROS production. Our results confirm that dopamine plays an important role in the regulation of insulin secretion by pancreatic beta cells through a regulated and precise compartmentalization mechanisms.

Asunto(s)

Comunicación Autocrina , Dopamina , Glucosa , Secreción de Insulina , Células Secretoras de Insulina , Insulina , Proteínas de Transporte Vesicular de Monoaminas , Insulina/metabolismo , Secreción de Insulina/efectos de los fármacos , Dopamina/metabolismo , Animales , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/efectos de los fármacos , Ratas , Glucosa/metabolismo , Comunicación Autocrina/efectos de los fármacos , Proteínas de Transporte Vesicular de Monoaminas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de Dopamina D2/metabolismo , Línea Celular , Tetrabenazina/farmacología , Tetrabenazina/análogos & derivados