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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

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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