INTERSTITIAL INSULIN CONCENTRATIONS DETERMINE GLUCOSE-UPTAKE RATES BUT NOT INSULIN-RESISTANCE IN LEAN AND OBESE MEN

Insulin action and obesity are both correlated with the density of mus cle capillary supply in humans. Since the altered muscle anatomy in th e obese might affect interstitial insulin concentrations and reduce in sulin action, we have cannulated peripheral lymphatic vessels in lean and obese males, and compared peripheral lymph insulin concentrations with whole body glucose uptake during a euglycemic, hyperinsulinemic c lamp. Lymph insulin concentrations in the lower limb averaged only 34% of arterial insulin concentrations during 150 min of insulin infusion . Obese subjects had the highest arterial (P less than or equal to 0.0 001) and lymph insulin (P < 0.005) concentrations, but the lowest gluc ose uptake rates (P < 0.002). In contrast to the initial steep rise th en plateau of arterial insulins, both lymph insulin and whole body glu cose uptake rates rose slowly and did not consistently reach a plateau . In each individual, the glucose uptake closely correlated with perip heral lymphatic insulin concentrations (mean r(2) = 0.95). The couplin g between glucose uptake and lymph insulin (glucose uptake/pmol insuli n) was much steeper in lean subjects than in the obese(P less than or equal to 0.0001). These results indicate that even if insulin diffusio n into tissues is rate limiting for insulin action, a tissue defect ra ther than an insulin diffusion defect causes insulin resistance in obe se subjects.