Horm Metab Res 2011; 43(1): 26-30
DOI: 10.1055/s-0030-1267169
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Metformin can Activate Imidazoline I-2 Receptors to Lower Plasma Glucose in Type 1-like Diabetic Rats

J.-P. Lee1 , W. Chen2 , H.-T. Wu3 , K.-C. Lin4 , 5 , J.-T. Cheng3 , 6
  • 1Department of Neurosurgery, Da Chien General Hospital, Miaoli City, Miaoli County, Taiwan
  • 2Department of Internal Medicine, E-Da Hospital and I-Shou University, Kaohsiung County, Taiwan
  • 3Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
  • 4Department of Neurology Chi-Mei Medical Center, Yong Kang City, Tainan County, Taiwan
  • 5Institute of Biotechnology, Southern Taiwan University, Yong Kang City, Tainan County, Taiwan
  • 6Department of Medical Research, Chi-Mei Medical Center, Yong Kang City, Tainan County, Taiwan
Further Information

Publication History

received 24.07.2010

accepted 08.09.2010

Publication Date:
13 October 2010 (eFirst)

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.

References

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