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Horm Metab Res 2011; 43(10): 708-713
DOI: 10.1055/s-0031-1286259
Original Basic
Georg Thieme Verlag KG Stuttgart · New York

Activation of Imidazoline I-2B Receptor by Metformin to Increase Glucose Uptake in Skeletal Muscle

C.-T Chen
1   Department of Pediatrics and Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan   
,
W. Chen
2   Department of Internal Medicine, E-Da Hospital and I-Shou University, Kaohsiung County, Taiwan   
,
H.-H Chung
3   Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan   
,
K.-C Cheng
4   Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima City, Japan
,
C.-H Yeh
5   Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan City, Taiwan   
,
J.-T Cheng
1   Department of Pediatrics and Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan   
3   Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan   
5   Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan City, Taiwan   
› Author Affiliations
Further Information

Publication History

received 13 July 2011

accepted 01 August 2011

Publication Date:
19 September 2011 (online)

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Abstract

Metformin (dimethylbiguanide) belongs to guanidinium-derivative and is widely used for treatment of diabetic disorders in clinic. Metformin lowers blood glucose in diabetic animals through increase of glucose uptake into skeletal muscle. Recent evidence indicates that activation of imidazoline I2B receptor (I2BR) by guanidinium-derivatives also increased glucose uptake; however, the effect of metformin on I2BR is still unknown. The blood glucose levels were determined by a glucose kit. The ability of glucose uptake into isolated skeletal muscle or cultured C2C12 cells was determined using 2-[14C]-deoxyglucose as tracer. The expressions of 5′ AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT-4) were identified by Western blotting analysis. The metformin-induced blood glucose-lowering action was dose-dependently blocked by BU224, a specific I2R antagonist, in Wistar rats. Also, similar reversion by BU224 was observed in isolated skeletal muscle regarding the metformin-induced glucose uptake. Moreover, AMPK phosphorylation by metformin was concentration-dependently reduced by BU224 in isolated skeletal muscle. In addition, signals for metformin increased glucose uptake were identified via I2R/PI3K/PKC/AMPK dependent pathway in C2C12 cells. Thus, we suggest that metformin can activate I2BR to increase glucose uptake and I2BR will be a new target for diabetic therapy.

Key words

5′ AMP-activated protein kinase - BU224 - diabetes - glucose transporter 4 - metformin
 

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