ROLE OF TISSUE-SPECIFIC BLOOD-FLOW AND TISSUE RECRUITMENT IN INSULIN-MEDIATED GLUCOSE-UPTAKE OF HUMAN SKELETAL-MUSCLE

Background-Conflicting evidence exist concerning whether insulin-induc ed vasodilation plays a mechanistic role in the regulation of limb glu cose uptake. It can be predicted that if insulin augments blood flow b y causing tissue recruitment, this mechanism would enhance limb glucos e uptake. Methods and Results-Twenty healthy subjects were studied wit h the forearm perfusion technique in combination with the euglycemic i nsulin clamp technique. Ten subjects were studied at physiological ins ulin concentrations (approximate to 400 pmol/L) and the other 10 at su praphysiological insulin concentrations (approximate to 5600 pmoI/L). Four additional subjects underwent a saline control study. Pulse injec tions of a nonmetabolizable extracellular marker (1-[H-3]-L-glucose) w ere administered into the brachial artery, and its washout curves were measured in one ipsilateral deep forearm Vein and used to estimate th e extracellular volume of distribution and hence the amount of muscle tissue drained by the deep forearm vein. Both during saline infusion a nd at physiological levels of hyperinsulinemia we observed no changes in blood flow and/or muscle tissue drained by the deep forearm vein. H owever, supraphysiological hyperinsulinemia accelerated total forearm blood flow (45.0+/-1.8 versus 36.5+/-1.3 mL.min(-1).kg(-1), P<0.01) an d increased the amount of muscle tissue drained by the deep forearm ve in (305+/-46 versus 229+/-32 g, P<0.05). The amount of tissue newly re cruited by insulin was strongly correlated to the concomitant increase in tissue glucose uptake (r=0.789, P<0.01). Conclusions-Acceleration of forearm blood flow mediated by supraphysiological hyperinsulinemia is accompanied by tissue recruitment, which may be a relevant determin ant of forearm (muscle) glucose uptake.