Involvement of α1 and β-adrenoceptors in adrenaline stimulation of the glucagon-secreting mouse α-cell
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Stimulation of glucagon release and inhibition of insulin secretion from the islets of Langerhans are important for the blood-glucose-elevating effect of adrenaline. The mechanisms by which adrenaline accomplishes these actions may involve direct effects and indirect ones mediated by altered release of other islet hormones. In the present study we investigated how adrenaline affects the cytoplasmic Ca2+ concentration, which controls glucagon secretion from the pancreatic α-cell. The studies were performed on isolated mouse α-cells, which were identified by immunocytochemistry.
The adrenaline effects consisted of initial mobilisation of intracellular Ca2+, accompanied by voltage-dependent influx of the ion. Part of the effect could be attributed to β-adrenoceptor activation, as it was mimicked by the rise in cAMP and inhibited by the antagonist propranolol as well as the protein kinase A inhibitor adenosine 3’,5’-cyclic monophosphorothioate Rp-isomer. α1-Adrenoceptors were also involved, since the antagonists phentolamine and prazosin completely abolished the effects of adrenaline. Experiments with clonidine and yohimbine gave little evidence of a role of α2-adrenoceptors. The results indicate that α1- and β-adrenoceptors on the α-cells mediate adrenaline-stimulated glucagon secretion. The complete inhibition of the adrenaline response after blocking α1-adrenoceptors indicates an interaction with the β-adrenergic pathway.
KeywordsGlucagon secretion α1-Adrenoceptors β-Adrenoceptors Calcium
This work was supported by grants from the Swedish Medical Research Council (12X-6240), the Swedish Foundation for Strategic Research, the Swedish Foundation for International Cooperation in Research and Higher Education, the Wenner-Gren Center Foundation, the Swedish Diabetes Association, Novo-Nordisk Foundation, Family Ernfors Foundation, the Scandinavian Physiological Society and the Swedish Society for Medical Research. Dr Vieira received a scholarship from the Amerique Latine Formation Academique (ALFA) program Islet Research European and Latin American Network (IRELAN) of the European Union.
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