Metformin increases insulin-stimulated glucose transport in insulin-resistant human skeletal muscle

The effect of metformin (0.1 mM) on glucose transport was investigated in healthy control and in insulin-resistant human skeletal muscle. Muscle samples (200-400 mg) were obtained from the rectus abdominis muscle (abdominal surgery) or from the vastus lateralis portion of the quadriceps femoris muscle (open biopsy technique) from 8 healthy controls (age 38 +/- 4 yrs, BMI 23 +/- 1) and from 6 insulin-resistant subjects (age 53 +/- 5 yrs, BMI 30 +/- 2). Metformin had no effect on basal or insulin-stimulated (100 microU/ml) 3-0-methylglucose transport in incubated muscle strips from healthy subjects. Muscle tissue from the insulin resistant group did not respond to 100 microU/ml of insulin (0.73 +/- 0.17 for basal and 0.81 +/- 0.22 mumol x ml-1 x h-1 for insulin-stimulation, NS). Basal glucose transport was unaffected by metformin, whereas insulin-stimulated (100 microU/ml) glucose transport was increased by 63% in the insulin-resistant muscles (0.73 +/- 0.17 in the absence vs 1.19 +/- 0.18 mumol x ml-1 x h-1 in the presence of metformin, p less than 0.05). In conclusion, metformin abolishes insulin-resistance in human skeletal muscle by normalizing insulin-stimulated glucose transport accross the muscle cell membrane. The mechanism for this effect remains to be elucidated.