title: Mechanisms of metformin action on glucose transport and metabolism in human adipocytes.
abstract: The mechanisms of metformin effects on glucose transport and metabolism were investigated in human adipocytes. Human preadipocytes obtained from surgical biopsies were differentiated in vitro into adipocytes and the effects of metformin on glucose uptake, glucose oxidation and the involved signaling pathways were analyzed. Metformin (1mM, 24h) increased glucose uptake 2.3±0.2-fold (p<0.001 vs. basal) in human adipocytes, without altering cell viability and oxygen consumption. Metformin did not alter GLUT-1 mRNA expression and protein content but increased GLUT-4 mRNA expression and cellular protein content, leading to increased GLUT-4 protein content in the plasma membrane. Neither basal nor insulin-induced phosphorylation of Akt at Ser-473 and AS160 (Akt substrate of 160kDa) at Thr-642 were enhanced by metformin. Suppression of metformin-induced AMP-activated protein kinase (AMPK) activity by AMPKα1 silencing, however, reduced metformin-associated GLUT-4 expression and stimulation of glucose uptake. In addition, metformin induced glucose oxidation. In conclusion, activation of AMPKα1 without impairment of cell respiration is crucial for metformin-mediated increase in GLUT-4 protein content and glucose uptake in human adipocytes.
authors.affiliation: Department of Biomedicine, Metabolism Group, Div. of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, CH-4031 Basel, Switzerland. jean.grisouard@unibas.ch
authors.forename: Jean
authors.initials: J
authors.lastname: Grisouard
authors.forename: Katharina
authors.initials: K
authors.lastname: Timper
authors.forename: Tanja M
authors.initials: TM
authors.lastname: Radimerski
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Frey
authors.forename: Ralph
authors.initials: R
authors.lastname: Peterli
authors.forename: Blerina
authors.initials: B
authors.lastname: Kola
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
authors.forename: Paul
authors.initials: P
authors.lastname: Herrmann
authors.forename: Stephan
authors.initials: S
authors.lastname: Krähenbühl
authors.forename: Henryk
authors.initials: H
authors.lastname: Zulewski
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D051275:Glucose Transporter Type 4; D008687:Metformin; D005947:Glucose