title: Canavanine activates imidazoline I-2 receptors to reduce hyperglycemia in type 1-like diabetic rats.
abstract: Canavanine is a guanidinium derivative that has the basic structure of a ligand for the imidazoline receptor (I-R). Furthermore, canavanine is found in an herb that has been shown to improve diabetic disorders. Thus, the present study was designed to investigate the anti-hyperglycemic action of canavanine in rats with streptozotocin (STZ)-induced type 1-like diabetes. Canavanine decreased hyperglycemia in the STZ-induced diabetic rats, and this action was blocked by the antagonist specific to imidazoline I-2 receptors (I-2R), BU224, in a dose-dependent manner. Additionally, canavanine increased the plasma β-endorphin level, as measured using enzyme-linked immunosorbent assay (ELISA), and this increase was also blocked by BU224 in the same manner. Moreover, amiloride at a dose sufficient to block I-2AR attenuated the actions of canavanine, including the increased β-endorphin level and the antihyperglycemic effect. Otherwise, canavanine increased the radioactive glucose uptake into skeletal muscles isolated from the diabetic rats. Furthermore, canavanine increased the phosphorylation of AMPK measured using Western blot analysis in these isolated skeletal muscles in a dose-dependent manner. Additionally, the insulin sensitivity of the diabetic rats was markedly increased by canavanine, and this action was also blocked by BU224. Overall, canavanine is capable of activating imidazoline I-2R; I-2AR is linked to an increase in the plasma level of β-endorphin, and I-2BR is related to effects on the glucose uptake by skeletal muscle that reduces hyperglycemia in type 1-like diabetic rats. Therefore, canavanine can be developed as effective agent to treat the diabetic disorders in the future.
authors.affiliation: Department of Neurosurgery, Chi-Mei Medical Center, Yong Kang, Tainan City 71003, Taiwan; Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City 71003, Taiwan.
authors.forename: Chin-Hong
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Bachelor Program of Senior Services, College of Humanities and Social Sciences, Southern Taiwan University of Science and Technology, Yong Kang, Tainan City 71005, Taiwan.
authors.forename: Pin-Chun
authors.initials: PC
authors.lastname: Chao
authors.affiliation: Department of Nursing, Tzu Chi College of Technology, Hualien City 97005, 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 70101, Taiwan.
authors.forename: Gin-Chi
authors.initials: GC
authors.lastname: Huang
authors.affiliation: Department of Nursing, Tzu Chi College of Technology, Hualien City 97005, 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 71003, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City 70101, Taiwan; Institute of Medical Sciences, Chang Jung Christian University, Guei-Ren, Tainan City 70101, Taiwan. Electronic address: jtcheng5503@yahoo.com.tw.
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002172:Canavanine / Q000494:pharmacology* / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D006943:Hyperglycemia / Q000188:drug therapy*; D054755:Imidazoline Receptors / Q000378:metabolism*; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D001615:beta-Endorphin / Q000097:blood
chemical_list: D054755:Imidazoline Receptors; C487767:imidazoline receptor 2; D002172:Canavanine; D001615:beta-Endorphin
keywords: Amiloride; Canavanine; Diabetes; Imidazoline receptor; β-endorphin