Summary
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 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 β-adrenergic receptors and that the α- and β-adrenergic receptors are at least partially interrelated.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Barrett, A.M., Cullum, V.A.: The biological properties of the optical isomers of propranolol and their effects on cardiac arrythmias, Brit. J. Pharmacol. 34, 43–55 (1968)
Burr, I.M., Balant, L., Stauffacher, W., Renold, R.E.: Adrenergic modification of glucose-induced biphasic insulin release from perifused rat pancreas. Europ. J. clin. Invest. 1, 216–224 (1971)
Cegrell, L.: The occurrence of biogenic monoamines in the mammalian endocrine pancreas. Acta physiol. scand., Suppl. 314, 5–60 (1968)
Ekholm, R., Ericson, L.E., Lundquist, I.: Monoamines in the pancreatic islets of the mouse. Subcellular localization of 5-hydroxytryptamine by electron microscopic autoradiography. Diabetologia 7, 339–349 (1971)
Ericson, L.E.: Uptake of 3H-5-hydroxytryptophan by noradrenergic nerves in the mouse pancreas studied with electron microscopic autoradiography. Z. Zellforsch. 113, 441–449 (1971)
Esterhuizen, A.C., Spriggs, L.B., Lever, M.D.: Nature of islet-cell innervation in the cat pancreas. Diabetes 17, 33–36 (1968)
Euler, U.S. v.: Release and uptake of noradrenaline in adrenergic nerve granules. Acta physiol. scand. 67, 430–440 (1966)
Feldman, J.M., Lebovitz, H.E.: Mechanism of epinephrine and serotonin inhibition of insulin release in the golden hamster in vitro. Diabetes 19, 480–487 (1970)
Haber, E., Wrenn, S.: Problems in identification of the beta-adrenergic receptor. Physiol. Rev. 56, 317–338 (1976)
Heding, L.G.: A simplified insulin radioimmunoassay method. In: Donato et al., Labelled proteins in tracer studies, pp. 345–350. Brussels: Euratom 1966
Honjin, F.: The innervation of the pancreas of the mouse with special reference to the structure of the peripheral extension of the vegetative nervous system. J. comp. Neurol. 104, 331–371 (1956)
Howe, R., Shanks, R.G.: Optical isomers of propranolol. Nature (Lond.) 210, 1336–1338 (1966)
Lundquist, I.: Insulin secretion. Its regulation by monoamines and acid amyloglucosidase. Acta physiol. scand., Suppl. 372, 1–47 (1971)
Lundquist, I.: Interaction of amines and aminergic blocking agents with blood glucose regulation. I. β- Adrenergic blockade. Europ. J. Pharmacol. 18, 213–224 (1972a)
Lundquist, I.: Interaction of amines and aminergic blocking agents with blood glucose regulation. II. α- Adrenergic blockade. Europ. J. Pharmacol. 18, 225–235 (1972b)
Malmfors, T.: Studies on adrenergic nerves. Acta physiol. scand., Suppl. 248, 7–93 (1965)
Marks, V.: An improved glucose-oxidase method for determining blood, C.S.F., and urinary glucose levels. Clin. chim. Acta 4, 395–401 (1959)
Orci, L., Perrelet, A., Ravazzola, M., Malaisse-Lagae, F., Renold, A.E.: A specialized membrane junction between nerve endings and B-cells in islets of Langerhans. Europ. J. clin. Invest. 3, 443–445 (1973a)
Orci, L., Unger, R.H., Renold, A.E.: Structural coupling between pancreatic islet cells. Experientia (Basel) 29, 1015–1018 (1973b)
Pappas, G.D., Asada, Y., Bennet, M.V.L.: Morphological correlates of increased coupling resistance at an electrotonic synapse. J. Cell Biol. 49, 173–188 (1971)
Porte, D., Jr.: Sympathetic regulation of insulin secretion and its relation to diabetes mellitus. Arch. intern. Med. 123, 252–260 (1969)
Porte, D., Jr., Robertson, R.P.: Control of insulin secretion by catecholamines, stress and the sympathetic nervous system. Fed. Proc. 32, 1792–1796 (1973)
Rerup, C., Lundquist, I.: Blood glucose level in mice. I. Evaluation of a new technique of multiple serial sampling. Acta endocr. (Kbh.) 52, 357–367 (1966)
Simpson, I, Rose, B., Loewenstein, W.R.: Size limit of molecules permeating the junctional membrane channels. Science 195, 294–296 (1977)
Smith, P.H., Porte, D., Jr.: Neuropharmacology of the pancreatic islets. Ann. Rev. Pharmacol. 16, 269–285 (1976)
Woods, S.C., Porte, D., Jr.: Neural control of the endocrine pancreas. Phys. Rev. 54, 596–618 (1974)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lundquist, I., Ericson, L.E. β-adrenergic insulin release and adrenergic innervation of mouse pancreatic islets. Cell Tissue Res. 193, 73–85 (1978). https://doi.org/10.1007/BF00221602
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00221602