edoc

Mechanisms of metformin action on glucose transport and metabolism in human adipocytes

Grisouard, Jean and Timper, Katharina and Radimerski, Tanja M. and Frey, Daniel M. and Peterli, Ralph and Kola, Blerina and Korbonits, Marta and Herrmann, Paul and Krahenbuhl, Stephan and Zulewski, Henryk and Keller, Ulrich and Muller, Beat and Christ-Crain, Mirjam. (2010) Mechanisms of metformin action on glucose transport and metabolism in human adipocytes. Biochemical Pharmacology, 80 (11). pp. 1736-1745.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A5841930

Downloads: Statistics Overview

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 AMPK?1 silencing, however, reduced metformin-associated GLUT-4 expression and stimulation of glucose uptake. In addition, metformin induced glucose oxidation. In conclusion, activation of AMPK?1 without impairment of cell respiration is crucial for metformin-mediated increase in GLUT-4 protein content and glucose uptake in human adipocytes.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Klinische Endokrinologie (Keller)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Klinische Endokrinologie (Keller)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie > Endokrinologie (Christ-Crain)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie > Endokrinologie (Christ-Crain)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Innere Organe
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Innere Organe
03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Metabolism (Keller/Müller)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmakologie (Krähenbühl)
UniBasel Contributors:Christ-Crain, Mirjam and Zulewski, Henryk and Peterli, Ralph and Keller, Ulrich O. and Krähenbühl, Stephan and Müller, Beat
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:0006-2952
e-ISSN:1873-2968
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:29 Nov 2017 11:24
Deposited On:26 Apr 2013 06:55

Repository Staff Only: item control page