Summary
Morphological changes in the adrenergic innervation of pancreatic islets after chemical sympathectomy by use of 6-hydroxydopamine and the influence of the sympatho-adrenal system on insulin secretion were investigated in the mouse and rat.
Fluorescence histochemistry revealed a clear-cut reduction in the number of adrenergic nerve fibers in the pancreatic islets 2 days after administration of 6-hydroxydopamine; the reduction was more pronounced in the rat than in the mouse. In the rat, a partial regeneration was seen after 6 weeks. In the pancreas of the mouse, after administration of 6-hydroxydopamine, a severe damage of unmyelinated nerve fibers was revealed electron microscopically. However, no ultrastructural or immunohistochemical alterations could be demonstrated in the endocrine cells of the islets.
6-Hydroxydopamine induced a depression of basal plasma insulin concentrations in mice and an elevation in rats. Adrenalectomy depressed basal plasma insulin levels in mice.
The α-adrenoceptor antagonist phentolamine enhanced insulin secretion in normal mice. The secretory response of insulin to phentolamine was diminished by chemical sympathectomy and almost abolished by adrenalectomy or the combination of chemical sympathectomy and adrenalectomy. Thus, the effect of phentolamine is probably mediated by liberated catecholamines.
It is concluded that basal insulin secretion is partially regulated by the sympatho-adrenal system and that species differences exist in this respect. In addition, the results suggest that endogenous catecholamines have the ability to promote insulin secretion.
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Ahrén B, Järhult J, Lundquist I (1981) Influence of the sympatho-adrenal system and somatostatin on the secretion of insulin in the rat. J Physiol in press
Ajelis V, Björklund A, Falck B, Lindvall O, Lorén I, Walles B (1979) Application of the aluminum-formaldehyde (ALFA) histofluorescence method for demonstration of peripheral stores of catecholamines and indolamines in freeze-dried paraffin-embedded tissue, cryostat sections and whole-mounts. Histochemistry 65:1–15
Björklund A, Falck B, Owman Ch (1972) Fluorescence microscopic and microspectrofluorometric techniques for the cellular localization and characterization of biogenic amines. In: Berson SA (ed) Methods of investigative and diagnostic endocrinology Vol I: Rall JR, Kopin IJ (eds) The thyroid and biogenic amines. North-Holland Publ Co, Amsterdam, pp 318–368
Bloom SR, Edwards AV (1975) The release of pancreatic glucagon and inhibition of insulin in response to stimulation of the sympathetic innervation. J Physiol 253:157–173
Bruss ML, Black AL (1978) Enzymatic microdetermination of glycogen. Anal Biochem 84:309–312
Burr IM, Jackson A, Culbert S, Sharp R, Felts P, Olson W (1974) Glucose intolerance and impaired insulin release following 6-hydroxydopamine administration to intact rats. Endocrinology 94:1072–1076
Cegrell L (1968) The occurrence of biogenic monoamines in the mammalian endocrine pancreas. Acta Physiol Scand Suppl 314:5–60
Coons AH, Leduc EM, Connolly JM (1955) Studies on antibody production. I. A method for the histochemical demonstration of specific antibodies and its application to a study of the hyperimmune rabbit. J Exp Med 102:49–59
Dairman W, Udenfriend S (1970) Effect of ganglionic blocking agents on the increased synthesis of catecholamines resulting from α-adrenergic blockade or exposure to cold. Biochem Pharmacol 19:979–984
Falck B, Hellman B (1964) A fluorescent reaction for monoamines in the insulin producing cells of the guinea-pig. Acta Endocr (Kbh) 45:133–138
Fredholm BB, Farnebo LO, Hamberger B (1978) Plasma catecholamines, cyclic AMP, and metabolic substrates in hemorrhagic shock of the rat. The effect of adrenal demedullation and 6-OH-dopamine treatment. Acta Physiol Scand 105:481–495
Gagliardino JJ, Bellone CF, Doria I, Sánchez JH, Pereyra V (1970) Adrenergic regulation of basal serum glucose, NEFA and insulin levels. Horm Metab Res 2:318–322
Gerich JE, Lorenzi M (1978) The role of the autonomic nervous system and somatostatin in the control of insulin and glucagon secretion. In: Ganong WF, Martini L (eds) Front Neuroendocr, Vol 5. Raven Press, New York, pp 265–288
Girardier L, Seydoux J, Berger M, Veicsteinas A (1978) Selective pancreatic nerve section. J Physiol Paris 74:731–735
Guicheney P, Meyer P (1979) Biochemical approach to pre and postsynaptic α-adrenoceptors. Trends Pharmacol Sci 1:69–70
Heding LG (1966) A simplified insulin radioimmunoassay method. In: Donato L, Milhaud G, Sirchis J (eds) Labelled proteins in tracer studies. Euratom Brussel, pp 345–350
Hertelendy F, Takahashi K, Machlin LJ, Kipnis DM (1970) The effect of chronic adrenergic blockade on the inhibition by epinephrine of growth hormone and insulin release in sheep. Horm Metab Res 2:257–259
Järhult J, Holst J (1979) The role of the adrenergic innervation of the pancreatic islets in the control of insulin release during exercise in man. Pflügers Arch 383:41–45
Järhult J, Ahrén B, Lundquist I (1979) Inhibitory effect of somatostatin on insulin secretion during α-adrenergic blockade in three different species Acta Endocr (Kbh) 92:166–173
Kostrzewa RM, Jacobowitz DM (1974) Pharmacological actions of 6-hydroxydopamine. Pharmacol Rev 26:199–288
Langer SZ (1974) Presynaptic regulation of catecholamine release. Biochem Pharmacol 23:1793–1800
Langer SZ (1977) Presynaptic receptors and their role in the regulatin of transmitter release. Br J Pharmacol 60:481–497
Larsson LI, Sundler F, Håkanson R (1976) Pancreatic polypeptide — a postulated new hormone: Identification of its cellular storage site by light and electron microscopic immunocytochemistry. Diabetologia 12:211–226
Lorén I, Björklund A, Falck B, Lindvall O (1980) The aluminum-formaldehyde (ALFA) histofluorescence method for improved visualization of catecholamines and indolamines. I. A detailed account of the methodology for central nervous tissue using paraffin, cryostat of Vibratome sections. J Neurosci Meth 2:277–300
Lorén I, Schmidt RM, Björklund A, Lindvall O, Falck B (1981) Improved catecholamine histofluorescence in the developing brain based on the magnesium and aluminum (ALFA) perfusion techniques: Methodology and anatomical observations. Neuroscience (to be published)
Loubatières-Mariani MM, Chapal J, Ribes G, Loubatières AL (1977) Discrepancies in the response of the insulin secreting cells of the dog and rat to different adrenergic stimulating agents. Acta Diabetol Lat 14:144–155
Lundquist I (1971) Insulin secretion. Its regulation by monoamines and acid amyloglucosidase. Acta Physiol Scand Suppl 372:5–47
Lundquist I (1972a) Interaction of amines and aminergic blocking agents with blood glucose regulation. I. β-Adrenergic blockade. Europ J Pharmacol 18:213–224
Lundquist I (1972b) Interaction of amines and aminergic blocking agents with blood glucose regulation. II. α-Adrenergic blockade. Europ J Pharmacol 18:225–235
Lundquist I, Ericson LE (1978) β-Adrenergic insulin release and adrenergic innervation of mouse pancreatic islets. Cell Tissue Res 193:73–85
Lundquist I, Sundler F, Ahrén B, Alumets J, Håkanson R (1979) Somatostatin, pancreatic polypeptide, substance P, and neurotensin: Cellular distribution and effects on insulin secretion in the mouse. Endocrinology 104:832–838
Porte Jr D (1967) A receptor mechanism for the inhibition of insulin release by epinephrine in man. J Clin Invest 46:86–94
Porte Jr D, Williams RH (1966) Inhibition of insulin release by norepinephrine in man. Science 152:1248–1250
Rerup C, Lundquist I (1966) Blood glucose level in mice. I. Evaluation of a new technique of multiple serial sampling. Acta Endocrinol (Kbh) 52:357–367
Schalch DS (1967) The influence of physical stress and exercise on growth hormone and insulin secretion in man. J Lab Clin Med 69:256–269
Smith PH, Woods SC, Porte Jr D (1976) Phentolamine blocks the somatostatin-mediated inhibition of insulin secretion. Endocrinology 98:1073–1076
Werrbach JH, Gale CC, Goodner CJ, Conway MJ (1970) Effects of autonomic blocking agents on growth hormone, insulin, free fatty acids and glucose in baboons. Endocrinology 86:77–82
Woods SC, Porte Jr D (1974) Neural control of the endocrine pancreas. Physiol Rev 54:596–619
Wright PH, Malaisse WJ (1968) Effects of epinephrine, stress and exercise on insulin secretion by the rat. Amer J Physiol 214:1031–1034
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Ahrén, B., Ericson, L.E., Lundquist, I. et al. Adrenergic innervation of pancreatic islets and modulation of insulin secretion by the sympatho-adrenal system. Cell Tissue Res. 216, 15–30 (1981). https://doi.org/10.1007/BF00234541
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DOI: https://doi.org/10.1007/BF00234541