Adrenalectomy and chemical sympathectomy by 6-hydroxydopamine. Effects on basal and stimulated insulin secretion
Influences of the sympatho-adrenal system on basal and stimulated insulin secretion were studied in vivo in the conscious mouse and rat.
In the mouse, adrenalectomy or chemical sympathectomy, induced by 6-hydroxydopamine, lowered basal insulin concentrations moderately. A marked depression of basal insulin concentration (about 50%) was seen after the combined treatment of chemical sympathectomy and adrenalectomy.
In short-term experiments in mice, insulin secretion stimulated by glucose or the cholinergic agonist carbachol was enhanced after chemical sympathectomy and/or adrenalectomy, whereas insulin release induced by the synthetic octapeptide of cholecystokinin (CCK-8) was inhibited. The promoting influences on the insulin secretory response to carbachol displayed a rapid development whereas those to glucose developed more slowly. In contrast, the inhibiting effect on CCK-8 stimulated insulin release vanished with time. The insulin secretory response to the β2 adrenoceptor stimulator, terbutaline, was increased after chemical sympathectomy, unaffected by adrenalectomy, and decreased after chemical sympathectomy plus adrenalectomy.
The glucose elimination rate after 6 weeks of chemical sympathectomy was increased in mice and decreased in rats. The insulin secretory response to glucose was enhanced in mice, whereas it tended to diminish in rats after long-term sympathectomy.
In conclusion, the sympatho-adrenal system is involved in regulation of basal insulin concentrations in the mouse, and apparently is of great importance for stimulated insulin secretion; the influence being dependent on the nature of the secretagogue.
Key wordsChemical sympathectomy Adrenalectomy Insulin secretion Glucose Carbachol CCK-8 Terbutaline Mouse Rat
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- 1.Ahrén B, Ericson LE, Lundquist I, Lorén I, Sundler F (in press) Adrenergic innervation of pancreatic islets and modulation of insulin secretion by the sympatho-adrenal system. Cell Tiss ResGoogle Scholar
- 2.Ahrén B, Järhult J, Lundquist I (in press) Influence of the sympathoadrenal system and somatostatin on the secretion of insulin in the rat. J Physiol (Lond)Google Scholar
- 3.Bloom SR, Edwards AV (1975) The release of pancreatic glucagon and inhibition of insulin in response to stimulation of the sympathetic innervation. J Physiol (Lond) 253:157–173Google Scholar
- 4.Brodows RG, Pi-Sunyer FX, Campbell RG (1974) Insulin secretion in adrenergic insufficiency in man. J Clin Endocrinol Metab 38:1103–1108Google Scholar
- 5.Bruss ML, Black AL (1978) Enzymatic microdetermination of glycogen. Anal Biochem 84:309–312Google Scholar
- 6.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 94:1072–1076Google Scholar
- 7.Cegrell L (1968) The occurrence of biogenic monoamines in the mammalian endocrine pancreas. Acta Physiol Scand Suppl 314:1–60Google Scholar
- 8.Esterhuizen AC, Springgs TLB, Lever MD (1968) Nature of islet-cell innervation in the cat pancreas. Diabetes 17:33–36Google Scholar
- 9.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 Neuroendocrinol, Vol 5. Raven Press, New York, pp 265–288Google Scholar
- 10.Girardier L, Seydoux J, Berger M, Veicsteinas A (1978) Selective pancreatic nerve section. An investigation of neural control of glucagon release in the conscious unrestrained dog. J Physiol (Paris) 74:731–735Google Scholar
- 11.Heding L (1966) A simplified insulin radioimmunoassay method. In: Donato L, Milhaud G, Sirchis J (eds) Labelled proteins in tracer studies. Euratom, Brussel, pp 345–350Google Scholar
- 12.Järhult J, Holst JJ (1978) Reflex adrenergic control of endocrine pancreas evoked by unloading of carotid baroreceptors in cats. Acta Physiol Scand 104:188–202Google Scholar
- 13.Järhult J, Holst J (1979) The role of the adrenergic innervation to the pancreatic islets in the control of insulin release during exercise in man. Pflügers Arch 383:41–45Google Scholar
- 14.Kostrzewa RM, Jacobowitz DM (1974) Pharmacological actions of 6-hydroxydopamine. Pharmacol Rev 26:199–288Google Scholar
- 15.Lundquist I (1971) Insulin secretion. Its regulation by monoamines and acid amyloglucosidase. Acta Physiol Scand Suppl 372:1–47Google Scholar
- 16.Lundquist I (1972) Interaction of amines and aminergic blocking agents with blood glucose regulation. II. α-Adrenergic blockade. Eur J Pharmacol 18:225–235Google Scholar
- 17.Lundquist I, Ericson LE (1978) β-Adrenergic insulin release and adrenergic innervation of mouse pancreatic islets. Cell Tiss Res 193:73–85Google Scholar
- 18.Miller RE (1975) Neural inhibition of insulin secretion from the isolated canine pancreas. Am J Physiol 229:144–149Google Scholar
- 19.Porte Jr D (1967) Beta adrenergic stimulation of insulin release in man. Diabetes 16:150–155Google Scholar
- 20.Porte Jr D (1967) A receptor mechanism for the inhibition of insulin release by epinephrine in man. J Clin Invest 46:86–94Google Scholar
- 21.Porte Jr D, William RH (1966) Inhibition of insulin release by norepinephrine in man. Science 152:1248–1250Google Scholar
- 22.Porte Jr D, Girardier L, Seydoux J, Kanazewa Y, Posternak J (1973) Neural regulation of insulin secretion in the dog. J Clin Invest 52:210–214Google Scholar
- 23.Rerup C, Lundquist I (1966) Blood glucose level in mice. I. Evaluation of a new technique of multiple serial sampling. Acta Endocrinol (Kbh) 52:357–367Google Scholar
- 24.Van Lan V, Yamaguchi N, Garcia MJ, Ramey ER, Penhos JC (1977) Effect of hypophysectomy and adrenalectomy on glucagon and insulin concentration. Endocrinology 94:671–675Google Scholar
- 25.Westfall TC (1977) Local regulation of adrenergic neurotransmission. Physiol Rev 57:659–728Google Scholar