title: Activation of AMPK improves inflammation and insulin resistance in adipose tissue and skeletal muscle from pregnant women.
abstract: Gestational diabetes mellitus (GDM) is characterised by maternal peripheral insulin resistance and inflammation. Sterile inflammation and bacterial infection are key mediators of this enhanced inflammatory response. Adenosine monophosphate (AMP)-activated kinase (AMPK), which is decreased in insulin resistant states, possesses potent pro-inflammatory actions. There are, however, no studies on the role of AMPK in pregnancies complicated by GDM. Thus, the aims of this study were (i) to compare the expression of AMPK in adipose tissue and skeletal muscle from women with GDM and normal glucose-tolerant (NGT) pregnant women; and (ii) to investigate the effect of AMPK activation on inflammation and insulin resistance induced by the bacterial endotoxin lipopolysaccharide (LPS) and the pro-inflammatory cytokine IL-1β. When compared to NGT pregnant women, AMPKα activity was significantly lower in women with GDM as evidenced by a decrease in threonine phosphorylation of AMPKα. Activation of AMPK, using two pharmacologically distinct compounds, AICAR or phenformin, significantly suppressed LPS- or IL-1β-induced gene expression and secretion of pro-inflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, and COX-2 and subsequent prostaglandin release from adipose tissue and skeletal muscle. In addition, activators of AMPK decreased skeletal muscle insulin resistance induced by LPS or IL-1β as evidenced by increased insulin-stimulated phosphorylation of IRS-1, GLUT-4 expression and glucose uptake. These findings suggest that AMPK may play an important role in inflammation and insulin resistance.
authors.affiliation: Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.|Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Melbourne, Victoria, Australia.
authors.forename: Stella
authors.initials: S
authors.lastname: Liong
authors.affiliation: Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia. mlappas@unimelb.edu.au.|Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Melbourne, Victoria, Australia. mlappas@unimelb.edu.au.|Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4/163 Studley Road, Heidelberg, Melbourne, 3084, Victoria, Australia. mlappas@unimelb.edu.au.
authors.forename: Martha
authors.initials: M
authors.lastname: Lappas
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016640:Diabetes, Gestational / Q000201:enzymology* / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000201:enzymology* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000276:immunology; D011247:Pregnancy; D046509:Tissue Culture Techniques
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000263:Adenylate Kinase; D005947:Glucose; D015232:Dinoprostone
keywords: AMPK; Adipose tissue; GDM; Infection; Inflammation; Insulin resistance; Skeletal muscle