Recent studies from our laboratory have shown that the rate at which insulin activates glucose disposal in vivo is much slower in obese subjects compared with lean controls. To determine if this was caused by an abnormality in activation of insulin-stimulated glucose transport at the cellular level, we measured the rate at which insulin stimulated glucose transport in human adipocytes from obese volunteers. Basal rates of 3-O-methylglucose transport in the absence of insulin were lower (0.20 ± 0.04 vs. 0.40 ± 0.11 pmol · 10−5 cells · 10 s−1P <.25) in adipocytes from obese subjects (n = 10) than in lean control subjects (n = 5), but this did not achieve statistical significance. Maximal insulin-stimulated (4300 pM insulin) glucose transport rates were significantly decreased in obesity (2.81 ± 0.81 vs. 1.15 ± 0.20 pmol · 10−5 cells · 10 S−1P < .005). It took longer for adipocytes from obese subjects to achieve half-maximal activation of insulin-stimulated glucose transport than those from lean subjects (15 ± 2 vs. 9.4 ± 1.2 min, P< .05). The slower overall rates of activation of maximal insulin-stimulated glucose transport observed in adipocytes from obese subjects mirror the slower rates of stimulation of glucose disposal in vivo, which suggests that the in vivo findings are caused by a cellular abnormality in insulin action at a step beyond the binding of insulin to its receptor. The decreased maximal rates of glucose uptake plus the slower rates of activation demonstrated in these studies combine to form an even greater degree of insulin resistance than might be expected from static measurements alone.

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