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.
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)
Matthaei
S
S
Department of Medicine, University-Hospital of Hamburg, Germany.
Hamann
A
A
Klein
H H
HH
Benecke
H
H
Kreymann
G
G
Flier
J S
JS
Greten
H
H
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
D001786:Blood Glucose; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D008687:Metformin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin