title: An active part of Artemisia sacrorum Ledeb. suppresses gluconeogenesis through AMPK mediated GSK3β and CREB phosphorylation in human HepG2 cells.
abstract: In this study, we investigated the effects of a petroleum ether fraction of Artemisia sacrorum Ledeb. (Compositae) (PEASL) on glucose production through AMP-activated protein kinase (AMPK) activation in human HepG2 cells. PEASL significantly inhibited glucose production in a concentration-dependent manner, and this effect was reversed in the presence of compound C, a selective AMPK inhibitor. PEASL markedly induced the phosphorylation of AMPK and downstream acetyl-CoA carboxylase (ACC) in a time- and concentration-dependent manner. In addition, it markedly increased the phosphorylations of glycogen synthase kinase 3β (GSK3β) in a concentration-dependent manner. In contrast, cAMP response element binding protein (CREB), a key transcription factor for gluconeogenic enzyme phosphorylation, decreased in a concentration-dependent manner. PEASL downregulated the gluconeogenesis gene expression of peroxisome proliferation activated receptor-γ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase) in a concentration-dependent manner. In addition, the gene expression of orphan nuclear receptor small heterodimer partner (SHP) increased, also in a concentration-dependent manner. These effects were also abolished by pretreatment with compound C, an AMPK inhibitor. This indicates that PEASL inhibited glucose production via the AMPK-GSK-CREB pathway in HepG2 cells, and these effects appeared to be capable of revealing anti-diabetic mechanism of PEASL in HepG2 cells.
authors.affiliation: Department of Pharmacognosy, College of Pharmacy, Yan Bian University, Yanji, Jilin Province, China.
authors.forename: Hai-Dan
authors.initials: HD
authors.lastname: Yuan
authors.forename: Guang-Chun
authors.initials: GC
authors.lastname: Piao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D019306:Artemisia / Q000737:chemistry*; D015153:Blotting, Western; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism; D038341:Glycogen Synthase Kinases / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D006360:Heat-Shock Proteins; D007004:Hypoglycemic Agents; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C099713:nuclear receptor subfamily 0, group B, member 2; D038341:Glycogen Synthase Kinases; D055372:AMP-Activated Protein Kinases; D005952:Glucose-6-Phosphatase; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D000103:Acetyl-CoA Carboxylase; D005947:Glucose