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Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
The aim of this study was to determine
barriers limiting muscle glucose uptake (MGU) during increased glucose
flux created by raising blood glucose in the presence of fixed insulin.
The determinants of the maximal velocity (Vmax)
of MGU in muscles of different fiber types were defined.
Conscious rats were studied during a 4 mU · kg
1 · min1
insulin clamp with plasma glucose at 2.5, 5.5, and 8.5 mM.
[U-14C]mannitol and
3-O-methyl-[3H]glucose ([3H]MG)
were infused to steady-state levels (t = 
180 to 0 min). These isotope infusions were continued from 0 to 40 min with the addition of a 2-deoxy-[3H]glucose ([3H]DG)
infusion. Muscles were excised at t = 40 min. Glucose
metabolic index (Rg) was calculated from
muscle-phosphorylated [3H]DG.
[U-14C]mannitol was used to determine extracellular (EC)
H2O. Glucose at the outer ([G]om) and inner
([G]im) sarcolemmal surfaces was determined by the ratio
of [3H]MG in intracellular to EC H2O and
muscle glucose. Rg was comparable at the two higher glucose
concentrations, suggesting that rates of uptake near
Vmax were reached. In summary, by defining the relationship of arterial glucose to [G]om and
[G]im in the presence of fixed hyperinsulinemia, it is
concluded that 1) Vmax for MGU is
limited by extracellular and intracellular barriers in type I fibers,
as the sarcolemma is freely permeable to glucose; 2) Vmax is limited in muscles with predominantly
type IIb fibers by extracellular resistance and transport resistance;
and 3) limits to Rg are determined by resistance
at multiple steps and are better defined by distributed control rather
than by a single rate-limiting step.
extracellular, intracellular water; glucose analogs; rat
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