title: Evidence that metformin increases insulin-stimulated glucose transport by potentiating insulin-induced translocation of glucose transporters from an intracellular pool to the cell surface in rat adipocytes.
abstract: To examine the cellular mechanism of the antihyperglycemic action of metformin (M) we studied the effect of M on various functional and molecular parameters involved in the pathogenesis of insulin resistance. Isolated rat adipocytes were incubated with or without M (1-100 micrograms/ml) for 2 hours at 37 degrees C followed by an incubation with or without insulin (I) (10) ng/ml). M-treatment had no significant effect on basal (B) 3-O-methylglucose uptake. In contrast, M increased I-stimulated glucose transport in a dose dependent manner up to 43 +/- 7%. This effect was neither associated with a significant effect of M on trace insulin binding, 1.74 +/- .2% (-M) vs 1.89 +/- .3% (+M), p > 0.05, nor with an effect of M on in vivo activation of insulin receptor kinase activity as measured by 32P-incorporation into the 95 kDa beta-subunit of the insulin receptor and an exogenous substrate, histone 2B.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University-Hospital of Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Matthaei
authors.forename: A
authors.initials: A
authors.lastname: Hamann
authors.forename: H H
authors.initials: HH
authors.lastname: Klein
authors.forename: H
authors.initials: H
authors.lastname: Benecke
authors.forename: G
authors.initials: G
authors.lastname: Kreymann
authors.forename: J S
authors.initials: JS
authors.lastname: Flier
authors.forename: H
authors.initials: H
authors.lastname: Greten
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin
chemical_list: D001786:Blood Glucose; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D008687:Metformin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin