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Journal of Clinical Endocrinology & Metabolism, Vol 70, 1525-1533, Copyright © 1990 by Endocrine Society
ARTICLES |
AD Baron, M Laakso, G Brechtel, B Hoit, C Watt and SV Edelman
Department of Medicine, Veterans Administration Medical Center, Indianapolis, Indiana 46202.
While it is well accepted that the disposal of an oral glucose load (OGL) occurs primarily in skeletal muscle, the mechanisms by which this occurs are not completely elucidated. Glucose uptake (GU) in skeletal muscle follows the Fick principal, such that GU equals the products of the arteriovenous glucose difference (AVGd) across and the blood flow (BF) into muscle. It is widely believed that in the postprandial period both insulin and glucose increase GU by increasing the AVGd; however, a role for increments in BF in the disposal and tolerance of an OGL has not been established. To investigate this issue, whole body GU (isotope dilution), leg GU (leg balance technique), leg BF, and cardiac index (CI) were measured after an overnight fast and over 180 min after an OGL (1 g/kg) in 8 lean (ln) and 8 obese (ob) subjects [mean +/- SEM age, 36 +/- 2 vs. 37 +/- 2 yr (P = NS) and 60 +/- 1 vs. 99 +/- 5 kg (P less than 0.01), respectively]. Serum glucose levels were higher in the ob than in the ln subjects between 100 and 160 min, indicating reduced glucose tolerance. Fasting and post-OGL serum insulin levels were 2- to 3-fold higher in ob vs. ln at all times, indicating insulin resistance. Peak (40-80 min) incremental whole body GU above baseline was 32% lower in ob vs. ln, (P less than 0.05). Peak femoral AVGd was not different between ob and ln (0.55 +/- 0.16 vs. 0.66 +/- 0.14 mmol/L; P = NS). Peak leg BF increased 36% over baseline in ln (0.328 +/- 0.052 to 0.449 +/- 0.073 L/min; P less than 0.05), while ob subjects displayed no change in leg BF from baseline. Consequently, peak leg GU was 44% lower in ob vs. ln (P less than 0.05). CI increased 24% from baseline at 60 min in ln (P less than 0.05), but was unchanged in ob. In summary, after an OGL 1) femoral AVGd increases in both ln and ob subjects, but skeletal muscle BF and CI increase in ln only; 2) since peak femoral AVGd values were similar in ln and ob, differences in peak leg GU and (by inference) whole body GU are largely due to reduced BF to insulin- sensitive tissues; and 3) hemodynamics play an important role in the physiological disposal of an OGL, and therefore, hemodynamic defects can potentially contribute to reduced glucose tolerance and insulin resistance.
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