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Horm Metab Res 2003; 35(4): 251-258
DOI: 10.1055/s-2003-39482
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Release of β-Endorphin by Caffeic Acid to Lower Plasma Glucose in Streptozotocin-Induced Diabetic Rats

J.  T.  Cheng 1 , I.  M.  Liu 1, 2 , T.  F.  Tzeng 3 , W.  C.  Chen 4 , S.  Hayakawa 4 , T.  Yamamoto 4
  • 1 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, R.O.C.
  • 2 Department of Pharmacy, Tajen Institute of Technology, Yen-Pou, Ping Tung Shien, Taiwan, R.O.C.
  • 3 Department of Internal Medicine, Pao Chien Hospital, Ping Tung City, Taiwan, R.O.C.
  • 4 Department of Obstetrics and Gynaecology, School of Medicine, Nihon University, Tokyo City, Japan.
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Publication History

Received 13 August 2002

Accepted after Revision 23 October 2002

Publication Date:
02 June 2003 (online)

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Abstract

The role of α1A-adrenoceptors in the regulation of opioid secretion from the adrenal glands of streptozotocin-induced diabetic rats (STZ-diabetic rats) was examined in an attempt to determine the mechanism of plasma glucose-lowering action of caffeic acid. In agreement with a previous report, we showed that caffeic acid produced a dose-dependent lowering of the plasma glucose concentration in STZ-diabetic rats along with an increase of plasma β-endorphin-like immunoreactivity (BER). These actions of caffeic acid were abolished by pretreatment with WB 4101 or RS 17 056 at doses sufficient to block α1A-adrenoceptors. In addition, naloxone and naloxonazine at doses effective for blocking opioid µ-receptors abolished the plasma glucose-lowering action of caffeic acid. Also, unlike that in wild-type diabetic mice, caffeic acid failed to produce a plasma glucose lowering effect in opioid µ-receptor knockout diabetic mice. We observed that caffeic acid could enhance BER release from isolated rat adrenal medulla in a concentration-dependent manner; inhibitors of α1A-adrenoceptors such as WB 4101 and RS 1705 abolished this action. Investigations of the signal pathways further supported that activation of α1A-adrenoceptor is responsible for the stimulatory effect of caffeic acid on BER secretion from the adrenal medulla. In the presence of U73312, a specific inhibitor of phospholipase C, the caffeic acid-induced increase of BER was reduced in a concentration-dependent manner, but it was not affected by U73343, the negative control of U73312. Chelerythrine and GF 109203X also diminished the action of caffeic acid at concentrations sufficient for inhibiting protein kinase C. Moreover, bilateral adrenalectomy in STZ-diabetic rats resulted in the loss of this plasma glucose-lowering effect of caffeic acid, and there was no increase in plasma BER with caffeic acid. Therefore, β-endorphin release from the adrenal gland appears to be responsible for the lowering of plasma glucose in STZ-diabetic rats induced by caffeic acid, through the activation of α1A-adrenoceptors.

Key words

Adrenal medulla - α1A-Adrenoceptor - β-Endorphin-like immunoreactivity - Caffeic acid - Phospholipase C - Protein kinase C

References

  • 1 Akil H, Watson S J, Young E, Lewis M E, Khachaturian H, Walker J M. Endogenous opioid: biology and function.  Annu Rev Neurosci. 1984;  7 223-255
    CrossrefPubMedGoogle Scholar
  • 2 Udenfriend S, Meienhofer J (Eds.). 1984 The peptide, Vo1 6, opioid peptides: biology, chemistry, and genetics. New York; Academic Press
    Google Scholar
  • 3 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
  • 4 Cheng J T, Liu I M, Tzeng T F, Tsai C C, Lai T Y. Plasma glucose lowering effect of β-endorphin in streptozotocin-induced diabetic rats.  Horm Metab Res. 2002;  34 570-576
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Furuta H. Direct evidence of alpha-adrenoceptor binding in rat and human adrenal glands. Nippon.  Hinyokika Gakkai Zasshi. 1990;  81 161-169
    PubMedGoogle Scholar
  • 6 Wikberg-Matsson A, Wikberg J E, Uhlen S. Characterization of alpha1-adrenoceptor subtypes in the pigs.  Eur J Pharmacol. 1998;  347 301-309
    CrossrefPubMedGoogle Scholar
  • 7 Ilcol Y O, Gurun M S, Taga Y, Ulus I H. Intraperitoneal administration of choline increases serum glucose in rat: involvement of the sympathoadrenal system.  Horm Meta Res. 2002;  34 341-347
    PubMedGoogle Scholar
  • 8 Cheng J T, Liu I M, Kuo D H, Lin M T. Stimulatory effect of phenylephrine on the secretion of β-endorphin from rat adrenal medulla in vitro. .  Auton Neurosci Basic & Clinic. 2001;  93 31-35
    PubMedGoogle Scholar
  • 9 Cai J F. 1995 Advanced textbook on traditional Chinese medicine and pharmacology, Vol. 2. Beijing; New World Press pp. 29-30
    Google Scholar
  • 10 Nardini M, D'Aquino M, Tomassi G, Gentili V, di Felice M, Scaccini C. Inhibition of human low-density lipoprotein oxidation by caffeic acid and other hydroxycinnamic acid derivatives.  Free Radic Biol Med. 1995;  19 541-552
    CrossrefPubMedGoogle Scholar
  • 11 Hsu F L, Chen Y C, Cheng J T. Caffeic acid as active principle from the fruit of Xanthium strumarium to lower plasma glucose in diabetic rats.  Planta Med. 2000;  66 228-230
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Cheng J T, Liu I M. Stimulatory effect of caffeic acid on α1A-adrenoceptors to increase glucose uptake into cultured C2C12 cells.  Naunyn-Schmiedebergs Arch Pharmacol. 2000;  362 122-127
    CrossrefPubMedGoogle Scholar
  • 13 Loh H H, Liu H C, Cavalli A, Yang W, Chen Y F, Wei L N. Opioid µ receptor knockout in mice: effects on ligand-induced analgesia and morphine lethality.  Mol Brain Res. 1998;  54 321-326
    CrossrefPubMedGoogle Scholar
  • 14 Liu I M, Chi T C, Shiao G C, Lin M T, Cheng J T. Loss of plasma glucose lowering response to cold stress in opioid mu-receptor knock-out diabetic mice.  Neurosci Lett. 2001;  307 81-84
    CrossrefPubMedGoogle Scholar
  • 15 Cheng J T, Liu I M, Chi T C, Tzeng T F. Release of β-endorphin by protaglandin E2 to lower plasma glucose in streptozotocin-induced diabetic rats.  Horm Metab Res. 2001;  33 439-443
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Vargo T, Rossier J, Minick S, Ling N, Rivier C, Vale W, Bloom F. β-Endorphin and adrenal corticotropin are secreted concomitantly by the pituitary gland.  Science. 1977;  197 1367-1369
    PubMedGoogle Scholar
  • 17 Hieble J P, Bylund D B, Clarke D E, Eikenburg D C, Langer S Z, Lefkowitz R J, Minneman K P, Ruffolo R R. X. Recommendation for nomenclature of alpha 1-adrenoceptors: consensus update. Pharmacol.  Rev. 1995;  47 267-270
    PubMedGoogle Scholar
  • 18 Zhong H, Minneman K P. α1-Adrenoceptor subtypes.  Eur J Pharmacol. 1999;  375 261-276
    CrossrefPubMedGoogle Scholar
  • 19 Goldstein A. Binding selectivity profiles for ligands of multiple receptor types: focus on opioid receptors.  Trends Pharmacol Sci. 1987;  8 456-459
    CrossrefPubMedGoogle Scholar
  • 20 Pasternak G W. Pharmacological mechanisms of opioid analgesics.  Clin Neuropharmacol. 1993;  16 1-18
    PubMedGoogle Scholar
  • 21 Martin W R. Opioid antagonists.  Pharmacol Rev. 1967;  19 463-521
    PubMedGoogle Scholar
  • 22 Ling G SF, Simantov R, Clark J A, Pasternak G W. Naloxonazine actions in vivo.  Eur J Pharmacol. 1986;  129 33-38
    CrossrefPubMedGoogle Scholar
  • 23 Cheng J T, Liu I M, Chi T C, Tzeng T F, Lu F H, Chang C J. Plasma glucose lowering effect of tramadol in streptozotocin-induced diabetic rats.  Diabetes. 2001;  50 2815-2821
    PubMedGoogle Scholar
  • 24 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
  • 25 Minneman K P, Han C, Abel P W. Comparison of α1-adrenergic receptor subtypes distinguished by chlorethylclonidine and WB 4101.  Mol Pharmacol. 1988;  33 509-514
    PubMedGoogle Scholar
  • 26 Marshall I, Burt R P, Green G M, Hussain M B, Chapple C R. Different subtypes of alpha 1A-adrenoceptor mediating contraction of rat epididymal vas deferens, rat hepatic portal vein and human prostate distinguished by the antagonist RS 17 053.  Br J Pharmacol. 1996;  119 407-415
    PubMedGoogle Scholar
  • 27 Arefolov V A, Dmitriev A D, Tennov A V, Val'dman A V. Detection of the pro-opiomelanocortin peptide fragments - beta-endorphin and ACTH-in the adrenals of rats and mice by immunohistochemistry.  Biull Eksp Biol Med. 1986;  101 445-447
    PubMedGoogle Scholar
  • 28 Mitsuma T, Nogimori T, Sun D H, Chaya M. Thyrotropin-releasing hormone reduces the plasma levels of beta-endorphin-like immunoreactivity in rats.  Exp Clin Endocrinol. 1987;  89 55-60
    PubMedGoogle Scholar
  • 29 Vatta M S, Presas M F, Bianciotti G, Rodriguez-Fermepin M, Ambros R, Fernandez B E. B and C types natriuretic peptides modify norepinephrine uptake and release in the rat adrenal medulla.  Peptides. 1997;  18 1483-1489
    CrossrefPubMedGoogle Scholar
  • 30 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
  • 31 Stratakis C A, Miller W R, Severin E, Chin K V, Bertherat J, Amieux P S, Eng C, Kammer G M, Dumont J E, Tortora G, Beaven M A, Puck T T, Jan d e, Weistein L S, Cho-Chung Y S. Protein-kinase A and human disease: the core of cAMP-dependent signaling in health and disease.  Horm Metab Res. 2002;  34 169-175
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Smallridge R C, Kiang J G, Gist I D, Fein H G, Gallowat R J. U-73122, an aminosteroid phospholipase C antagonist, noncompetitively inhibits thyrotropin-releasing hormone effects in GH3 rat pituitary cell.  Endocrinology. 1992;  131 1883-1888
    CrossrefPubMedGoogle Scholar
  • 33 Muto Y, Nagao T, Urushidani T. The putative phospholipase C inhibitor U73122 and its negative control, U73343, elicit unexpected effects on the rabbit parietal cell.  J Pharmac Exp Ther. 1997;  282 1379-1388
    PubMedGoogle Scholar
  • 34 de Moel M P, van de Put F H, Vermegen T M, de Pont J H, Willems P H. Effect of the aminosteroid, U73122, on Ca2+ uptake and release properties of rat liver microsomes.  Eur J Biochem. 1995;  234 626-631
    CrossrefPubMedGoogle Scholar
  • 35 Wang J P, Hsu M F, Kuo S C. Inhibition by abruquinone A of phosphoinositide-specific phospholipase C activation in rat neutrophils.  Eur J Pharmacol. 1997;  319 131-136
    CrossrefPubMedGoogle Scholar
  • 36 Herbert J M, Augereau J M, Gleye J, Maffrand J P. Chelerythrine is a potent and specific inhibitor of protein kinase C.  Biochem Biophys Res Commun. 1990;  172 993-999
    CrossrefPubMedGoogle Scholar
  • 37 Toullec D, Pianetti P, Coste H, Bellevergue P, Grand-Perret T, Ajakane M, Baudent V, Boissin P, Boursier E, Loriolle F, Duhamel L, Charon D, Kirilovsky J. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C.  J Biol Chem. 1991;  266 15 771-15 781
    PubMedGoogle Scholar

Prof. J. T. Cheng

Department of Pharmacology · College of Medicine · National Cheng Kung University

Tainan City · Taiwan 70101 · R.O.C. ·

Phone: +886(6)2372706

Fax: +886(6)2386548

Email: jtcheng@mail.ncku.edu.tw

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