β-adrenergic insulin release and adrenergic innervation of mouse pancreatic islets.

An investigation of the stereospecificity of β-adrenergic insulin release, its relation to α-adrenergic blockade and the adrenergic innervation of the pancreatic islets was performed in the mouse. It was observed that in vivo β-adrenergic stimulation of insulin release by isopropylnoradrenaline was stereospecific for the L-stereoisomer and selectively blocked by the L-isomer of the β-adrenergic antagonist L-propranolol. D-propranolol had no effect. Pretreatment of mice with a dose of D-isopropylnoradrenaline devoid of insulin releasing activity, slightly increased the subsequent insulin response to a halfmaximal dose of L-isopropylnoradrenaline. Basal insulin secretion was blocked by L-propranolol ( β-adrenergic blockade) and increased by phentolamine ( α-adrenergic blockade). A β-blocked insulin response to L-isopropyl-noradrenaline could be overcome by α-adrenergic blockade depending on the dose of the β-agonist, suggesting a close association between the adrenergic receptors. The adrenergic innervation of the islet cells was studied by electron microscopic autoradiography after injection of H-L-noradrenaline. It was observed that labelled adrenergic nerve terminals were associated with both A(D-), A and B-cells. The nerves were mainly distributed in the periphery of the islets either as single axons or as bundles. The majority of the terminals were associated with A-cells, the most frequent cell type in the islet periphery. However, in all islets examined terminals were found close to B-cells. Adrenergic terminals often caused indentations in the contour of an islet cell and were separated from the islet cell membrane only by a narrow intercellular space, about 20 nm in width. It is concluded that the islet cells of the mouse are equipped with the morphological substrate for direct adrenergic regulation. Further it is suggested that the B-cell is supplied with L-stereospecific β-adrenergic receptors and that the α- and β-adrenergic receptors are at least partially interrelated. [ABSTRACT FROM AUTHOR]