Ae. Halseth et al., Limitations to basal and insulin-stimulated skeletal muscle glucose uptakein the high-fat-fed rat, AM J P-ENDO, 279(5), 2000, pp. E1064-E1071
Citations number
45
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Rats fed a high-fat diet display blunted insulin-stimulated skeletal muscle
glucose uptake. It is not clear whether this is due solely to a defect in
glucose transport, or if glucose delivery and phosphorylation are also impa
ired. To determine this, rats were fed standard chow (control rats) or a hi
gh-fat diet (HF rats) for 4 wk. Experiments were then performed on consciou
s rats under basal conditions or during hyperinsulinemic euglycemic clamps.
Rats received primed constant infusions of 3-O-methyl-[H-3] glucose (3-O-M
G) and [1-C-14]mannitol. Total muscle glucose concentration and the steady-
state ratio of intracellular to extracellular 3-O-MG concentration [which d
istributes based on the transsarcolemmal glucose gradient (TSGG)] were used
to calculate glucose concentrations at the inner and outer sarcolemmal sur
faces ([G](im) and [G](om), respectively) in soleus. Total muscle glucose w
as also measured in two fast-twitch muscles. Muscle glucose uptake was mark
edly decreased in HF rats. In control rats, hyperinsulinemia resulted in a
decrease in soleus TSGG compared with basal, due to increased [G](im). In H
F rats during hyperinsulinemia, [G](im) also exceeded zero. Hyperinsulinemi
a also decreased muscle glucose in HF rats, implicating impaired glucose de
livery. In conclusion, defects in extracellular and intracellular component
s of muscle glucose uptake are of major functional significance in this mod
el of insulin resistance.