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DOI: 10.1055/s-0030-1267169
© Georg Thieme Verlag KG Stuttgart · New York
Metformin can Activate Imidazoline I-2 Receptors to Lower Plasma Glucose in Type 1-like Diabetic Rats
Publication History
received 24.07.2010
accepted 08.09.2010
Publication Date:
13 October 2010 (online)

Abstract
Metformin is widely used in clinic for handling the diabetic disorders. However, action mechanisms of metformin remain obscure. It has recently been indicated that guanidinium derivatives are ligands to activate type-2 imidazoline receptors (I-2 receptors) that can improve diabetes through increment in skeletal muscle glucose uptake. Also, activation of I-2 receptors can increase the release of ß-endorphin in diabetic animals. Because metformin is a guanidinium derivative, we were interested in the effect of metformin on I-2 receptors. In the present study, the marked blood glucose-lowering action of metformin in streptozotocin-induced type-1 like diabetes rats was blocked by specific I-2 receptor antagonist, BU224, in a dose-dependent manner. Also, the increase of ß-endorphin release by metformin was blocked by BU224 in same manner. A specific competition between metformin and BU224 was observed in isolated adrenal medulla. Otherwise, amiloride at the dose sufficient to block I-2A receptor abolished the metformin-induced ß-endorphin release, but only the blood glucose-lowering action of metformin was markedly reduced. In addition, the blood glucose-lowering action of metformin in bilateral adrenalectomized rats was diminished by amiloride at higher doses. These results suggest that metformin might activate imidazoline I-2 receptors while I-2A receptors link the increase of ß-endorphin release and I-2B receptors couple to the other actions for lowering of blood glucose in type-1 like diabetic rats.
Key words
amiloride - β-endorphin - diabetes - imidazoline receptor - metformin
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Correspondence
Prof. J.-T.Cheng
Department of Medical
Research
Chi-Mei Medical Center
Yong Kang City
Tainan County
Taiwan 73101
Phone: +886/6/331 8516
Fax: +886/6/238 6548
Email: m980103@mail.chimei.org.tw
Prof. K.-C. Lin
Department of Neurology
Chi-Mei Medical Center
Yong Kang City
Tainan County
Taiwan 73101
Phone: +886/6/281 2811
Fax: +886/6/238 6548
Email: aauiana@mail2000.org.tw