HYPOXIA STIMULATES GLUCOSE-TRANSPORT IN INSULIN-RESISTANT HUMAN SKELETAL-MUSCLE

Insulin and muscle contraction stimulate glucose transport into muscle cells by separate signaling pathways, and hypoxia has been shown to o perate via the contraction signaling pathway. To elucidate the mechani sm of insulin resistance in human skeletal muscle, strips of rectus ab dominis muscle from lean (body mass index [BMI] < 25), obese (BMI > 30 ), and obese non-insulin-dependent diabetes mellitus (NIDDM) (BMI > 30 ) patients were incubated under basal and insulin-, hypoxia-, and hypo xia + insulin-stimulated conditions, Insulin significantly stimulated 2-deoxyglucose transport approximately twofold in muscle from lean (P < 0.05) patients, but not in muscle from obese or obese NIDDM patients , Furthermore, maximally insulin-stimulated transport rates in muscle from obese and diabetic patients were significantly lower than rates i n muscle from lean patients (P < 0.05), Hypoxia significantly stimulat ed glucose transport in muscle from lean and obese patients, There wer e no significant differences in hypoxia-stimulated glucose transport r ates among lean, obese, and obese NIDDM groups. Hypoxia + insulin sign ificantly stimulated glucose transport in lean, obese, and diabetic mu scle, The results of the present study suggest that the glucose transp ort effector system is intact in diabetic human muscle when stimulated by hypoxia.