beta-Adrenergic insulin release and adrenergic innervation of mouse pancreatic islets

Abstract

An investigation of the stereospecificity of beta-adrenergic insulin release, its relation to alpha-adrenergic blockade and the adrenergic innervation of the pancreatic islets was performed in the mouse. It was observed that in vivo beta-adrenergic stimulation of insulin release by isopropylnoradrenaline was stereospecific for the L-stereoisomer and selectively blocked by the L-isomer of the beta-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 half-maximal dose of L-isopropylnoradrenaline. Basal insulin secretion was blocked by L-propranolol (beta-adrenergic blockade) and increased by phentolamine (alpha-adrenergic blockade). A beta-blocked insulin response to L-isopropyl-noradrenaline could be overcome by alpha-adrenergic blockade depending on the dose of the beta-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 3H-L-noradrenaline. It was observed that labelled adrenergic nerve terminals were associated with both A1- (D-), A2- 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 A2-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 beta-adrenergic receptors and that the alpha- and beta-adrenergic receptors are at least partially interrelated.