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Horm Metab Res 2001; 33(7): 439-443
DOI: 10.1055/s-2001-16236
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Release of β-Endorphin by Prostaglandin E2 to Lower Plasma Glucose in Streptozotocin-Induced Diabetic Rats

J. T. Cheng 1 , I. M. Liu 1 , T. C. Chi 1 , T. F. Tzeng 2
  • 1 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, R.O.C.
  • 2 Department of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan, R.O.C.
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Publication History

Publication Date:
31 December 2001 (online)

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In the present study, Wistar rats, which received a streptozotocin injection to induce diabetes (STZ-diabetic rats), a model similar to insulin-dependent diabetes mellitus (IDDM) or type 1 diabetes mellitus, were used to investigate the effect of prostaglandin (PG) E2 on plasma glucose. Intravenous injection of PGE2 produced a dose-dependent lowering of plasma glucose level in fasting STZ-diabetic rats after 60 min. In addition to the blockade of this hypoglycemic effect by guanethidine (a noradrenergic nerve terminal-blocking agent), prazosin at a dose effective to block α1-adrenoceptors abolished the action of PGE2. An increase of plasma norepinephrine (NE) was also observed in STZ-diabetic rats receiving PGE2 injections. Participation of sympathetic stimulation by PGE2 may thus be speculated. Also, the plasma glucose-lowering effect of PGE2 was also blocked by pretreatment with naloxone or naloxonazine at doses sufficient to block opioid µ-receptor. Injection of PGE2 increased plasma β-endorphin-like immunoreactivity (BER) in STZ-diabetic rats, and this action was abolished by prazosin. Bilateral adrenalectomy resulted in the loss of this PGE2 effect, and no increase was seen in plasma BER with PGE2 in STZ-diabetic rats. Therefore, β-endorphin from the adrenal gland appears to be responsible for the lowering of plasma glucose in STZ-diabetic rats by PGE2 through an increase of NE release to activate α1-adrenoceptors.

Key words:

α1-Adrenoceptor - β-Endorphin - PGE2 - Diabetic Rats

References

  • 1 Robertson R R, Chen M. A role for prostaglandin E in defective insulin secretion and carbohydrate intolerance in diabetes mellitus.  J Clin Invest. 1977;  60 747-753
    PubMedGoogle Scholar
  • 2 Robertson R P. Hypothesis: Eicosanoids as pluripotential modulators of pancreatic islet function.  Diabetes. 1988;  34 367-370
    PubMedGoogle Scholar
  • 3 Farber H W, Barnett H F. Differences in prostaglandin metabolism in cultured aortic and pulmonary arterial endothelial cells exposed to acute and chronic hypoxia.  Circ Res. 1991;  68 1446-1457
    PubMedGoogle Scholar
  • 4 Williamson J R, Chang K, Frangos M, Hasan K S, Ido Y, Kawamura T, Nyengaard J R, van den Enden M, Kilo C, Tilton R G. Hyperglycemic pseudohypoxia and diabetic complications.  Diabetes. 1993;  42 801-813
    CrossrefPubMedGoogle Scholar
  • 5 Schambelan M, Blake S. Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus.  J Clin Invest. 1985;  75 404-412
    PubMedGoogle Scholar
  • 6 Tesfamariam B, Brown M L, Deykin D, Cohen R A. Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoid in rabbit aorta.  J Clin Invest. 1990;  85 929-932
    PubMedGoogle Scholar
  • 7 Yatomi A, Iguchi A, Yanagisawa S, Matsunaga H, Niki I, Sakamoto N. Prostaglandins affect the central nervous system to produce hyperglycemia in rat.  Endocrinology. 1987;  121 36-41
    PubMedGoogle Scholar
  • 8 Liu I M, Niu C S, Chi T C, Kuo D H, Cheng J T. Investigations of the mechanism of the reduction of plasma glucose by cold-stress in streptozotocin-induced diabetic rats.  Neurosci. 1999;  92 1137-1142
    CrossrefPubMedGoogle Scholar
  • 9 Liu I M, Chi T C, Chen Y C, Lu F H, Cheng J T. Activation of opioid µ-receptor by loperamide to lower plasma glucose in streptozotocin-induced diabetic rats.  Neurosci Lett. 1999;  265 183-186
    CrossrefPubMedGoogle Scholar
  • 10 Forman L J, Estilow S, Mead J, Vasilenko P. Eight weeks of streptozotocin-induced diabetes influences the effects of cold stress on immunoreactive beta-endorphin levels in female rats.  Horm Metabol Res. 1988;  20 555-558
    PubMedGoogle Scholar
  • 11 Chang S L, Lin J G, Chi T C, Liu I M, Cheng J T. An insulin-dependent hypoglycemia induced by electroacupuncture at the Zhongwan (CV12) acupoint in diabetic rats.  Diabetologia. 1999;  42 250-255
    CrossrefPubMedGoogle Scholar
  • 12 Koenig J I, Meltzer H Y, Devane G D, Gudelsky G A. The concentration of arginine vasopressin in pituitary stalk plasma of the rat after adrenalectomy or morphine.  Endocrinology. 1986;  118 2534-2539
    PubMedGoogle Scholar
  • 13 Martin W R. Opioid antagonists.  Pharmacol Rev. 1967;  19 463-521
    PubMedGoogle Scholar
  • 14 Ling G SF, Simantov R, Clark J A, Pasternak G W. Naloxonazine actions in vivo. .  Eur J Pharmacol. 1986;  129 33-38
    CrossrefPubMedGoogle Scholar
  • 15 Johansen O, Tønnesen T, Jensen T, Burhol P G, Jorde R, Reikeras O. Morphine and morphine/naloxone modification of glucose, glucagon and insulin levels in fasted and fed rats.  Scand J Clin Lab Invest. 1993;  53 805-809
    PubMedGoogle Scholar
  • 16 Rahman W, Dashwood N R, Fitzgerald M, Aynsley-Green A, Dickenson A H. Postnatal development of multiple opioid receptors in the spinal cord and development of spinal morphine analgesia.  Brain Res Dev Brain Res. 1998;  108 239-254
    CrossrefPubMedGoogle Scholar
  • 17 Bartolome J V, Bartolome M B, Harris E B, Pauk J S, Schanberg S M. Regulation of insulin and glucose plasma levels by central nervous system beta-endorphin in preweanling rats.  Endocrinology. 1989;  124 2153-2158
    PubMedGoogle Scholar
  • 18 Ipp E, Dobbs R, Unger R H. Morphine and beta-endorphin influence the secretion of the endocrine pancreas.  Nature. 1978;  276 190-191
    PubMedGoogle Scholar
  • 19 Reid R L, Yen S SC. β-Endorphin stimulates the secretion of insulin and glucagon in diabetes mellitus.  Metabolism. 1984;  33 197-199
    CrossrefPubMedGoogle Scholar
  • 20 McCubbin J A, Surwit R S, Williams R B, Nemeroff C B, McNeilly M. Altered pituitary hormone response to naloxone in hypertension development.  Hypertension. 1989;  14 636-644
    PubMedGoogle Scholar
  • 21 Naranjo J R, Urdin M C, Borrell J, Fuentes J A. Evidence for a central but not adrenal, opioid mediation in hypertension induced by brief isolation in the rat.  Life Sci. 1986;  38 1923-1930
    CrossrefPubMedGoogle Scholar
  • 22 Yang H -YT, Hexum T, Costa E. Minireview: opioid peptides in adrenal gland.  Life Sci. 1980;  27 1119-1125
    CrossrefPubMedGoogle Scholar
  • 23 Leslie F M, Kosteerlize H W. Comparison of binding of [3H]-methionine-enkephalin, [3H]-naltrexone and [3H]-dihydromorphine in the mouse vas deferens and the myenteric plexus and brain of the guinea pig.  Eur J Pharmac. 1979;  56 379-383
    PubMedGoogle Scholar
  • 24 Vlaskovska M, Knepel W. Beta-endorphin and adrenocorticotropin release from rat adrenohypophysis in vitro: Evidence for local modulation by arachidonic acid metabolites of the cyclooxygenase and lipoxygenase pathway.  Neuroendocrinology. 1984;  39 334-342
    PubMedGoogle Scholar
  • 25 Knepel W, Gotz D. Effect of prostaglandin E2 on ACTH and β-endorphin release from rat adenohypophysis in vitro after secretagogues which can mimic various first or second messengers.  Naunyn-Schmiedeberg’s Arch Pharmacol. 1986;  333 149-155
    PubMedGoogle Scholar
  • 26 Halushka P V, Lurie D, Colwell J A. Increased synthesis of prostaglandin-E-like material by platelets from patients with diabetes mellitus.  N Engl J Med. 1977;  297 1306-1331
    PubMedGoogle Scholar

Prof. Juei-Tang Cheng

Department of Pharmacology
College of Medicine
National Cheng Kung University

Tainan City
Taiwan 70101, R.O.C.


Phone: + 886-6-237-2706

Fax: + 886-6-238-6548

Email: jtcheng@mail.ncku.edu.tw