title: Effects of N-adamantyl-4-methylthiazol-2-amine on hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats.
abstract: Thiazole derivatives are attractive candidates for drug development because they can be efficiently synthesized and are active against a number of diseases and conditions, including diabetes. In our present study, we investigated the anti-inflammatory and antioxidant properties of N-adamantyl-4-methylthiazol-2-amine (KHG26693), a new thiazole derivative, in a streptozotocin (STZ)-induced model of diabetes mellitus. STZ-induced diabetic rats were intraperitoneally administered KHG26693 (3mg/kg-body weight/day) for 4 weeks. KHG26693 administration significantly decreased blood glucose, triglycerides, and cholesterol and increased insulin. KHG26693 also suppressed several inflammatory responses in STZ-induced diabetic rats, as evidenced by decreased levels of serum tumor necrosis factor-α, interleukin-1β, and nitric oxide. Additionally, KHG26693 significantly modulated hepatic lipid peroxidation, catalase and superoxide dismutase activity, and the nonenzymatic antioxidant status (e.g., vitamins C and E), and reduced the glutathione content. These anti-inflammatory/antioxidative actions occurred as a result of the downregulation of inducible nitric oxide synthase and nuclear factor-kappa B. Taken together, our results suggest that KHG26693 successfully reduces the production of oxidative stress in STZ-induced diabetic rats by regulating the oxidation-reduction system, specifically increasing antioxidant capacity. Furthermore, KHG26693 treatment significantly reverted the key enzymes of glucose metabolism, such as glucokinase, glucose-6-phosphatase, glycogen synthase, glycogen phosphorylase, and fructose-1,6-bisphosphatase, to near-normal levels in liver tissues. These results indicate that KHG26693 normalizes disturbed glucose metabolism by enhancing glucose utilization and decreasing liver glucose production via insulin release, suggesting the possibility of future diabetes treatments.
authors.affiliation: Department of Biomedical Laboratory Science, Konyang University, Daejeon 302-718, Republic of Korea.
authors.forename: Seung-Ju
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Woo
authors.initials: W
authors.lastname: Je Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-gu, Seoul 138-736, Republic of Korea.
authors.forename: Eun-A
authors.initials: EA
authors.lastname: Kim
authors.affiliation: Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul 136-791, Korea.
authors.forename: Kee
authors.initials: K
authors.lastname: Dal Nam
authors.affiliation: Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul 136-791, Korea.
authors.forename: Hoh-Gyu
authors.initials: HG
authors.lastname: Hahn
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Republic of Korea.
authors.forename: Soo
authors.initials: S
authors.lastname: Young Choi
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-gu, Seoul 138-736, Republic of Korea. Electronic address: swcho@amc.seoul.kr.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D053583:Interleukin-1beta / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D053583:Interleukin-1beta; C000594799:N-adamantyl-4-methylthiazol-2-amine; D016328:NF-kappa B; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D014810:Vitamin E; D009569:Nitric Oxide; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D000218:Adamantane; D001205:Ascorbic Acid
keywords: Antioxidant; Diabetes; Inflammation; Oxidative stress; Thiazole derivative