Summary
As shown previously clonidine reduces glucose-stimulated insulin release and this effect is mediated by inhibitory postsynaptic α2-adrenoceptors.
The present experiments demonstrate that clonidine has the additional property to also stimulate insulin release. This became evident when the a2-adrenoceptors of isolated islets were blocked by benextramine, and thus protected from being stimulated by clonidine.
In the presence of benextramine, clonidine no longer reduced, but on the contrary enhanced, the release of insulin in response to glucose. In control experiments benextramine by itself failed to affect insulin release from isolated islets.
These results show that the imidazoline derivative clonidine shares the property of other imidazoline compounds to enhance the insulin response to glucose. All of these agents may stimulate insulin by binding to “imidazoline-preferring” sites, that clearly differ from α-adrenoceptors.
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References
Andersson T, Nygren P (1983) Clonidine promotes the accumulation of45Ca in pancreatic β-cell organelles. Res Com Chem Path Pharmacol 42:369–376
Coupry I, Podevin RA, Dausse J-P, Parini A (1987) Evidence for imidazoline binding sites in basolateral membranes from rabbit kidney. Biochem Biophys Res Corn 147:1055–1060
Ernsberger P, Meeley MP, Mann JJ, Reis DJ (1987) Clonidine binds to imidazole binding sites as well as α2-adrenoceptors in the ventrolateral medulla. Eur J Pharmacol 134:1–13
Garcia-Morales P, Dufrane SP, Sener A, Valverde I, Malaisse WJ (1984) Inhibitory effect of clonidine upon adenylate cyclase activity, cyclic AMP production, and insulin release in rat pancreatic islets. Biosci Rep 4:511–521
Gorewit RC(1980) Effects of clonidine on glucose production and insulin secretion of cattle. Am J Vet Res 41:1769–1772
Hamilton CA, Reid JL, Yakubu MA (1988) [3H]Yohimbine and [3H]idazoxan bind to different sites on rabbit forebrain and kidney membranes. Eur J Pharmacol 146:345–348
Humphreys MH, Reid IA (1979) Effects of clonidine on glucose and phosphate metabolism in the anesthetized dog. J Pharmacol Exp Ther 208:243–247
Ismail NA, El-Denshary ESM, Idahl L-A, Lindström P,Sehlin J, Täaljedal 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
Iwata Y (1969) Hyperglycemic action of 2-(2, 6-dichlorphenylamino)-2-imidazoline hydrochloride in relation to its hypertensive effect. Jpn J Pharmacol 19:249–259
Lal S, Tolis G, McDonald TJ, Cervantes P, Dupré J (1981) Effect of clonidine on growth hormone and glucagon secretion. Horm Metabol Res 13:648–649
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
Laychock SG (1987) α2-Adrenoceptor stimulation affects total glucose utilization in isolated islets of Langerhans. Mol Pharmacol 32:241–248
Leclercq-Meyer V, Herchuelz A, Valverde I, Couturier E, Marchand J, Malaisse WJ (1980) Mode of action of clonidine upon islet function. Diabetes 29:193–200
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
Melchiorre C (1981) Tetramine disulfides: anew tool in α-adrenergic pharmacology. Trends Pharmacol Sci 3:209–211
Metz SA, Halter JB, Robertson RP (1978) Induction of defective insulin secretion and impaired glucose tolerance by clonidine. Diabetes 27:554–562
Michel MC, Brodde O-E, Schnepel B, Behrendt J, Tschada R, Motulsky HJ, Insel PA (1989) [3H]Idazoxan and some other α2-adrenergic drugs also bind with high affinity to a nonadrenergic site. Mol Pharmacol 35:324–330
Nakadate T, Nakaki T, Muraki T, Kato R (1980) Regulation of plasma insulin level by α2-adrenergic receptors. Eur J Pharmacol 65:421–424
Nakaki T, Nakadate T, Kato R (1980) α2-Adrenoceptors modulating insulin release from isolated pancreatic islets. NaunynSchmiedeberg's Arch Pharmacol 313:151–153
Nilsson T, Arkhammar P, Rorsman P, Berggren P-O (1987) Inhibition of glucose-stimulated insulin release by α2-adrenoceptor activation is parallelled by both a repolarization and a reduction in cytoplasmic free Ca2+ concentration. J Biol Chem 263: 1855–1860
Schulz A, Hasselblatt A (1988) Phentolamine, a deceptive tool to investigate sympathetic nervous control of insulin release. Naunyn-Schmiedeberg's Arch Pharmacol 337:637–643
Schulz A, Hasselblatt A (1989) An insulin releasing property of imidazoline derivatives is not limited to compounds that block α-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 340:321–327
Wilcoxon F (1945) Individual comparisons by ranking methods. Biometrics 1:80–83
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Schulz, A., Hasselblatt, A. Dual action of clonidine on insulin release: suppression, but stimulation when α2-adrenoceptors are blocked. Naunyn-Schmiedeberg's Arch. Pharmacol. 340, 712–714 (1989). https://doi.org/10.1007/BF00717749
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DOI: https://doi.org/10.1007/BF00717749