Skip to main content
SpringerLink
Log in

Phentolamine, a deceptive tool to investigate sympathetic nervous control of insulin release

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

We investigated the effects of phentolamine and another more selective α2-adrenoceptor antagonist, rauwolscine, on insulin release in vivo (in female Wistar-rats) and in vitro (in perfused rat pancreas and in isolated perifused mouse islets). Phentolamine was found to significantly increase glucose-induced insulin release. On the other hand, rauwolscine failed to do so, when applied in a concentration that effectively antagonized the inhibitory effect of clonidine. These results demonstrate that phentolamine is capable of directly stimulating insulin release. This effect is thus not mediated by α-adrenoceptors. For this reason phentolamine is not an appropriate tool to study possible inhibitory effects of the sympathetic nervous system on insulin release. An enhanced insulin response as may be observed in animals and in man in the presence of phentolamine does not furnish evidence for a tonic inhibitory control of the islet cells by the sympathetic nervous system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ahrén B, Ericson LE, Lundquist I, Lorén I, Sundler F (1981) Adrenergic innervation of pancreatic islets and modulation of insulin secretion by the sympatho-adrenal system. Cell Tissue Res 216:15–30

    Google Scholar 

  • Ahrén B, Lundquist I, Järhult J (1984) Effects of α1-, α2- and β-adrenoceptor blockers on insulin secretion in the rat. Acta Endocrinol 105:78–82

    Google Scholar 

  • Ahrén B, Lundquist I (1985) Effects of α-adrenoceptor blockade by phentolamine on basal and stimulated insulin secretion in the mouse. Acta Physiol Scand 125: 211–217

    Google Scholar 

  • Al-Jibouri LM, Furman BL, Parrat JR (1980) Blockade of adrenaline-induced hyperglycaemia in the anaesthetized cat by continuous infusion of phentolamine and propranolol. Br J Pharmacol 68:461–466

    Google Scholar 

  • Andersson P-O, Holst J, Järhult J (1982) Effects of adrenergic blockade on the release of insulin, glucagon and somatostatin from the pancreas in response to splanchnic nerve stimulation in cats. Acta Physiol Scand 116:403–409

    Google Scholar 

  • Basabe JC, Cresto JC, Aparicio N (1977) Studies on the mode of action of somatostatin on insulin secretion. Endocrinology 101:1436 -1443

    Google Scholar 

  • Broadstone VL, Pfeifer MA, Bajaj V, Stagner JI, Samols E (1987) α-Adrenergic blockade improves glucose-potentiated insulin secretion in non-insulin-dependent diabetes mellitus. Diabetes 36:932–937

    CAS  PubMed  Google Scholar 

  • Buse MG, Johnson AH, Kuperminc D, Buse J (1970) Effect of α-adrenergic blockade on insulin secretion in man. Metabolism 19:219–225

    Google Scholar 

  • Cerasi E, Efendić S, Luft R (1969) Role of adrenergic receptors in glucose-induced insulin secretion in man. Lancet 2:301–302

    Google Scholar 

  • Coore HG, Randle PJ (1964) Regulation of insulin secretion studied with pieces of rabbit pancreas incubated in vitro. Biochem J 93:66–78

    Google Scholar 

  • Doxey JC, Roach AG, Smith CFC (1983) Studies on RX 781094: a selective, potent and specific antagonist of α2-adrenoceptors. Br J Pharmacol 78:489–505

    Google Scholar 

  • Efendić S, Cerasi E, Luft R (1973) Effect of blockade of the α-adrenergic receptors on insulin response to glucose infusion in prediabetic subjects. Acta Endocrinol 74:542–547

    Google Scholar 

  • Frohman LA, Ezdinli EZ, Javid R (1967) Effect of vagotomy and vagal stimulation on insulin secretion. Diabetes 16:443–448

    Google Scholar 

  • Fyles JM, Cawthorne MA, Howell SL (1986) The characteristics of β-adrenergic binding sites on pancreatic islets of Langerhans. J Endocrinol 111:263–270

    Google Scholar 

  • Gagliardino JJ, Bellone CF, Doria I, Sánchez JJ, Pereyra V (1970) Adrenergic regulation of basal and serum glucose, NEFA and insulin levels. Horm Metabol Res 2:318–322

    Google Scholar 

  • Grodsky GM, Batts AA, Bennett LL, Vcella C, McWilliams NB, Smith PF (1963) Effects of carbohydrates on secretion of insulin from isolated rat pancreas. Am J Physiol 205:638–644

    Google Scholar 

  • Guthrie GP Jr, Miller RE, Kotchen TA, Koenig SH (1983) Clonidine in patients with diabetes and mild hypertension. Clin Pharmacol Ther 34:713–717

    Google Scholar 

  • Hasselblatt A (1987) Wird auch unter Ruhebedingungen die Insulinabgabe durch einen dauernden hemmenden sympathischen Tonus gedrosselt? In: Mehnert H, Schlierf G, Schöffling K (eds) Akt Endokrin Stoffw 8:81–82

  • Ismail NA, El-Denshary ESM, Idahl L-Å, Lindström P, Sehlin J, Täljedahl I-B (1983) Effects of alpha-adrenoceptor agonists and antagonists on insulin secretion, calcium uptake and rubidium efflux in mouse pancreatic islets. Acta Physiol Scand 118:167–174

    Google Scholar 

  • Joost HG (1979) Effects of a possible beta-cell membrane label, metahexamide-isothiacyanate, on insulin release. Horm Metabol Res 11:104–106

    Google Scholar 

  • Kansal PC, Buse MG (1967) The effect of adrenergic blocking agents on plasma insulin and blood glucose during urethan or epinephrine induced hyperglycemia. Metabolism 16:548–556

    Google Scholar 

  • Kris AO, Miller RE, Wherry FE, Mason JW (1966) Inhibition of insulin secretion by infused epinephrine in rhesus monkeys. Endocrinology 78:87–97

    Google Scholar 

  • Langer J, Panten U, Zielmann S (1983) Effects of α-adrenoceptor antagonists on clonidine-induced inhibition of insulin secretion by isolated pancreatic islets. Br J Pharmacol 79:415–420

    Google Scholar 

  • Leclercq-Meyer V, Herchuelz A, Valverde I, Couturier E, Marchand J, Malaisse WJ (1980) Mode of action of clonidine upon islet function. Dissociated effects upon the time course and magnitude of insulin release. Diabetes 29:193–200

    Google Scholar 

  • Lenzen S (1979) Insulin secretion by isolated perfused rat and mouse pancreas. Am J Physiol 236(4):E391-E400

    Google Scholar 

  • Lernmark Å (1974) The preparation of, and studies on, free cell suspensions from mouse pancreatic islets. Diabetologia 10: 431–438

    Google Scholar 

  • Linde J, Deckert T (1973) Increase of insulin concentration in maturity-onset diabetics by phentolamine (regitin) infusion. Horm Metab Res 5:391–395

    Google Scholar 

  • Lundquist I (1972) Interaction of amines and aminergic blocking agents with blood glucose regulation. II. α-Adrenergic blockade. Eur J Pharmacol 18:225–235

    Google Scholar 

  • Malaisse W, Malaisse-Lagae F, Wright PH, Ashmore J (1967) Effects of adrenergic and cholinergic agents upon insulin secretion in vitro. Endocrinology 80:975–978

    Google Scholar 

  • Mann HB, Whitney DR (1947) On a test of whether one of two random variables is stochastically larger than the other. Ann Math Statist 18:50–60

    Google Scholar 

  • Marliss BE, Wollheim CB, Blondel B, Orci L, Lambert AE, Stauffacher W, Like AA, Renold AE (1973) Insulin and glucagon release from monolayer cell cultures of pancreas from newborn rats. Eur J Clin Invest 3:16–26

    Google Scholar 

  • Meguid MM, Moore Ede MC, Fitzpatrick G, Moore FD (1975) Norepinephrine-induced insulin and substrate changes in normal man: incomplete reversal by phentolamine. J Surg Res 18:365–369

    Google Scholar 

  • Metz SA, Halter JB, Robertson RP (1978) Induction of defective insulin secretion and impaired glucose tolerance by clonidine. Diabetes 27:554–562

    Google Scholar 

  • Misbin RI, Edgar PJ, Lockwood DH (1970) Adrenergic regulation of insulin secretion during fasting in normal subjects. Diabetes 19:688–693

    Google Scholar 

  • Nakadate T, Nakaki T, Muraki T, Kato R (1980) Adrenergic regulation of blood glucose levels: possible involvement of postsynaptic alpha-2 type adrenergic receptors regulating insulin release. J Pharmacol Exp Ther 215:226–230

    Google Scholar 

  • Nakaki T, Nakadate T, Kato R (1980) α2-Adrenoceptors modulating insulin release from isolated pancreatic islets. Naunyn-Schmiedeberg's Arch Pharmacol 313:151–153

    Google Scholar 

  • Nakaki T, Nakadate T, Ishii K, Kato R (1981) Postsynaptic alpha-2 adrenergic receptors in isolated rat islets of Langerhans: inhibition of insulin release and cyclic 3′:5′-adenosine monophosphate accumulation. J Pharmacol Exp Ther 216:607–612

    Google Scholar 

  • Oda S, Ohtomo Y, Ohneda A, Sasaki Y, Tsuda T (1986) Adrenergic modulation of pancreatic glucagon and insulin secretion in goats. Comp Biochem Physiol 84:723–728

    Google Scholar 

  • Panten U, Ishida H, Schauder P, Frerichs H, Hasselblatt A (1977) A versatile microperifusion system. Anal Biochem 82:317–326

    Google Scholar 

  • Porte D Jr, Graber AL, Kuzuya T, Williams RH (1966) The effect of epinephrine on immunoreactive insulin levels in man. J Clin Invest 45:228–236

    Google Scholar 

  • Porte D Jr (1967) A receptor mechanism for the inhibition of insulin release by epinephrine in man. J Clin Invest 46:86–94

    Google Scholar 

  • Porte D Jr (1969) Sympathetic regulation of insulin secretion. Arch Intern Med 123:252–260

    Google Scholar 

  • Robertson RP, Porte D Jr (1973) Adrenergic modulation of basal insulin secretion in man. Diabetes 22:1–8

    Google Scholar 

  • Robertson RP, Halter JB, Porte D Jr (1976) A role for α-adrenergic receptors in abnormal insulin secretion in diabetes mellitus. J Clin Invest 57:791–795

    Google Scholar 

  • Schuit FC, Pipeleers DG (1986) Differences in adrenergic recognition by pancreatic A and B cells. Science 232:875–877

    Google Scholar 

  • Starke K (1981) α-Adrenoceptor subclassification. Rev Phys Biochem Pharmakol 88:199–236

    Google Scholar 

  • Struthers AD, Brown DC, Brown MJ, Schamer B, Bloom SR (1985) Selective α2 receptor blockade facilitates the insulin response to adrenaline but not to glucose in man. Clin Endocrinol 23: 539–546

    Google Scholar 

  • Trapold JH, Warren MR, Woodbury RA (1950) Pharmacological and toxicological studies on 2-(N-p′-tolyl-N-(m′-hydroxy-phenyl)-aminomethyl)-imidazoline (C-7337), a new adrenergic blocking agent. J Pharmacol 100:119–127

    Google Scholar 

  • Wilcoxon F (1945) Individual comparisons by ranking methods. Biometrics 1:80–83

    Google Scholar 

  • Woods SC, Porte D Jr (1974) Neural control of the endocrine pancreas. Physiol Rev 54:596–619

    Google Scholar 

  • Zielmann S, Schütte G, Lenzen S, Panten U (1985) Effects of isoprenaline and glucagon on insulin secretion from pancreatic islets. Naunyn-Schmiedeberg's Arch Pharmacol 329:299–304

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie, Universität Göttingen, Robert-Koch-Strasse 40, D-3400, Göttingen, Germany

    A. Schulz & A. Hasselblatt

Authors
  1. A. Schulz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Hasselblatt
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Some of the results have been published in a preliminary form (Hasselblatt A 1987)

Send offprint requests to A. Schulz at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schulz, A., Hasselblatt, A. Phentolamine, a deceptive tool to investigate sympathetic nervous control of insulin release. Naunyn-Schmiedeberg's Arch Pharmacol 337, 637–643 (1988). https://doi.org/10.1007/BF00175789

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00175789

Key words

Search

Navigation