D. Galuska et al., EFFECT OF METFORMIN ON INSULIN-STIMULATED GLUCOSE-TRANSPORT IN ISOLATED SKELETAL-MUSCLE OBTAINED FROM PATIENTS WITH NIDDM, Diabetologia, 37(8), 1994, pp. 826-832
Citations number
31
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Metformin has been demonstrated to lower blood glucose in vivo by a me
chanism which increases peripheral glucose uptake. Furthermore, the th
erapeutic concentration of metformin has been estimated to be in the o
rder of 0.01 mmol/l. We investigated the effect of metformin on insuli
n-stimulated 3-O-methylglucose transport in isolated skeletal muscle o
btained from seven patients with non-insulin-dependent diabetes mellit
us (NIDDM) and from eight healthy subjects. Whole body insulin-mediate
d glucose utilization was decreased by 45 % (p < 0.05) in the diabetic
subjects when studied at 8 mmol/l glucose, compared to the healthy su
bjects studied at 5 mmol/l glucose. Metformin, at concentrations of 0.
1 and 0.01 mmol/l, had no effect on basal or insulin-stimulated (100 m
u U/ml) glucose transport in muscle strips from either of the groups.
However, the two control subjects and three patients with NIDDM which
displayed a low rate of insulin-mediated glucose utilization (< 20 mu
mol.kg(-1).min(-1)), as well as in vitro insulin resistance, demonstra
ted increased insulin-stimulated glucose transport in the presence of
metformin at 0.1 mmol/l (p < 0.05). In conclusion, the concentration o
f metformin resulting in a potentiating effect on insulin-stimulated g
lucose transport in insulin-resistant human skeletal muscle is 10-fold
higher than the therapeutic concentrations administered to patients w
ith NIDDM. Thus, it is conceivable that the hypoglycaemic effect of me
tformin in vivo may be due to an accumulation of the drug in the extra
cellular space of skeletal muscle, or to an effect of the drug distal
to the glucose transport step.