Document Detail


Mechanisms of metformin action on glucose transport and metabolism in human adipocytes.
MedLine Citation:
PMID:  20816671     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Jean Grisouard; Katharina Timper; Tanja M Radimerski; Daniel M Frey; Ralph Peterli; Blerina Kola; Márta Korbonits; Paul Herrmann; Stephan Krähenbühl; Henryk Zulewski; Ulrich Keller; Beat Müller; Mirjam Christ-Crain
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-08
Journal Detail:
Title:  Biochemical pharmacology     Volume:  80     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2010-11-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1736-45     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Biomedicine, Metabolism Group, Div. of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, CH-4031 Basel, Switzerland. jean.grisouard@unibas.ch
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / drug effects*,  metabolism*
Adult
Aged
Biological Transport / drug effects,  physiology
Cell Survival / drug effects,  physiology
Cells, Cultured
Female
Glucose / metabolism*
Glucose Transporter Type 4 / metabolism
Humans
Male
Metformin / pharmacology*
Middle Aged
Oxygen Consumption / drug effects,  physiology
Signal Transduction / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Glucose Transporter Type 4; 50-99-7/Glucose; 657-24-9/Metformin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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