title: Canavanine increases glucose uptake in C2 C12 cells through the activation of imidazoline I-2B receptors.
abstract: Canavanine is a guanidinium derivative that contains the basic structure of the ligand(s) of imidazoline receptor (I-R). Canavanine has been reported to activate the imidazoline I-3 receptor (I-3R) both in vivo and in vitro. Additionally, the activation of the imidazoline I-2B receptor (I-2BR) by guanidinium derivatives may increase glucose uptake. Therefore, the effect of canavanine on the I-2BR was investigated in the present study. Glucose uptake into cultured C2 C12 cells was determined using the radio-ligated tracer 2-[(14) C]-deoxy-glucose. The changes in 5' AMP-activated protein kinase (AMPK) expression were also identified using Western blotting analysis. The canavanine-induced glucose uptake was inhibited in a dose-dependent manner by BU224 (0.01-1 μmol/L), which is a specific I-2BR antagonist, in the C2 C12 cells. Additionally, the canavanine-stimulated AMPK phosphorylation and glucose transporter (GLUT4) expression were also sensitive to BU224 inhibition in the C2 C12 cells. Moreover, both canavanine-stimulated glucose uptake and AMPK phosphorylation were attenuated by high concentrations of amiloride (1-2 μmol/L), which is another established I-2BR inhibitor, in a dose-dependent manner in C2 C12 cells. Additionally, compound C abolished the canavanine-induced glucose uptake and AMPK phosphorylation at a concentration (0.1 μmol/L) sufficient to inhibit AMPK. In conclusion, these data demonstrated that canavanine has an ability to activate I-2BR through the AMPK pathway to increase glucose uptake, which indicates I-2BR as a new target for diabetic therapy.
authors.affiliation: Bachelor Program of Senior Services, College of Humanities and Social Sciences, Southern Taiwan University of Science and Technology, Yong Kang, Tainan City, Taiwan.
authors.forename: Pin-Chun
authors.initials: PC
authors.lastname: Chao
authors.affiliation: Department of Neurosurgery, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan.|Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan.
authors.forename: Chin-Hong
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Nursing, Tzu Chi College of Technology, Hualien City, Taiwan.
authors.forename: Ho-Shan
authors.initials: HS
authors.lastname: Niu
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
authors.forename: Gin-Chi
authors.initials: GC
authors.lastname: Huang
authors.affiliation: Department of Nursing, Tzu Chi College of Technology, Hualien City, Taiwan.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan.|Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.|Institute of Medical Sciences, Chang Jung Christian University, Guei-Ren, Tainan City, Taiwan.
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002172:Canavanine / Q000494:pharmacology*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D054755:Imidazoline Receptors / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D051275:Glucose Transporter Type 4; D054755:Imidazoline Receptors; D002172:Canavanine; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: 5′ AMP-activated protein kinase; BU224; canavanine; glucose uptake; imidazoline receptor