title: A novel indole derivative compound GY3 improves glucose and lipid metabolism via activation of AMP-activated protein kinase pathway.
abstract: The AMP-activated protein kinase (AMPK) is a ubiquitously expressed serine/threonine protein kinase that functions as an intracellular fuel sensor. It has been demonstrated to mediate the activities of a number of pharmacological and physiological factors that exert beneficial effects on type2 diabetes mellitus. GY3 is a novel synthesized indole compound derived from indomethacin, a non-steroid anti-inflammatory drug. In a previous study, we found that GY3 could improve insulin resistance and lower glucose levels in db/db mice, although its mechanism of action is not yet clear. In this study, we demonstrate that in vivo administration of GY3 improved serum triglyceride levels and decreased lipid accumulation in the livers of db/db mice. In vitro studies show that GY3 increased glucose consumption in HepG2 cells and 3T3-L1 adipocytes, decreased free fatty acid (FFA)-induced lipid accumulation in HepG2 cells and lipid accumulation in 3T3-L1 adipocytes. In vitro studies further show that GY3 improved glucose and lipid metabolism through an AMPK-dependent pathway but not the PI3K pathway. These findings suggest that GY3 is an effective agent for the improvement of glucose and lipid metabolism through AMPK pathway activation.
authors.affiliation: Institute of Pharmacology & Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yu-hang-tang Road, Hangzhou 310058, China.
authors.forename: Meimei
authors.initials: M
authors.lastname: Si
authors.forename: Youyou
authors.initials: Y
authors.lastname: Yan
authors.forename: Lei
authors.initials: L
authors.lastname: Tang
authors.forename: Honghai
authors.initials: H
authors.lastname: Wu
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: He
authors.forename: Haoshu
authors.initials: H
authors.lastname: Wu
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007210:Indoleacetic Acids / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014280:Triglycerides / Q000097:blood
chemical_list: C526371:1-(4-chlorobenzoyl)-5-hydroxy-2-methyl-3-indoleacetic acid; D005230:Fatty Acids, Nonesterified; D007210:Indoleacetic Acids; D014280:Triglycerides; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D005947:Glucose