DECREASED INSULIN-STIMULATED 3-0-METHYLGLUCOSE TRANSPORT IN INVITRO INCUBATED MUSCLE STRIPS FROM TYPE-II DIABETIC SUBJECTS

Peripheral insulin resistance in type II diabetes mellitus has been attributed to alterations in skeletal muscle glucose metabolism. However the direct dose-response relationship between insulin and glucose transport has not yet been studied in human skeletal muscle. We investigated 3-0-methylglucose transport in in vitro incubated skeletal muscle strips from eight healthy controls (age 61 +/- 6 yrs) and six lean type II diabetic patients treated with oral antidiabetic medication (age 73 +/- 3 yrs). Rectus abdominis muscle samples (approximately 1 g), obtained during elective abdominal surgery, were clamped at their resting length in vivo, whereupon strips (20-50 mg) were prepared for in vitro incubation. Measurements of high-energy phosphates and glycogen levels revealed that the muscle strips maintained energy levels during the incubation period. Glucose transport responded to insulin in a dose-response manner in the control group, with a 2-fold increase following maximal stimulation. Muscle strips from the diabetic group demonstrated a marked decrease in the insulin dose-response curve (P < 0.01), when compared to healthy muscle strips. At a maximal insulin concentration (10,000-mu-U x ml-1), the response of the diabetic muscle tissue was 50% less than that of the healthy control tissue (P < 0.05). This report demonstrates a dose-response curve for insulin stimulated 3-0-methylglucose transport in in vitro incubated human skeletal muscle strips. Furthermore, in type II diabetic muscle, our results provide evidence for one or several defects at a postreceptor level.