Jk. Kim et al., METABOLIC IMPAIRMENT PRECEDES INSULIN-RESISTANCE IN SKELETAL-MUSCLE DURING HIGH-FAT FEEDING IN RATS, Diabetes, 45(5), 1996, pp. 651-658
Citations number
38
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
To examine whether impairment of intracellular glucose metabolism prec
edes insulin resistance, we determined the time courses of changes in
insulin-stimulated glucose uptake, glycolysis, and glycogen synthesis
during high-fat feeding in rats. Animals were fed with a high-fat (66.
5%) diet ad libitum for 0, 2, 4, 7, or 14 days (n = 10-11 in each grou
p) after 5 days of a low-fat (12.5%) diet. Submaximal and maximal insu
lin-stimulated glucose fluxes were estimated in whole body and individ
ual skeletal muscles using the glucose clamp technique combined with D
-[3-H-3]glucose infusion and 2-[1-C-14]deoxyglucose injection. Both su
bmaximal and maximal insulin-stimulated glucose uptake in whole body d
ecreased gradually with high-fat feeding, However, the decreases were
minimal and not statistically significant during the initial few days
(i.e., 2 and 4 days) of high-fat feeding (P > 0.05). In contrast, insu
lin-stimulated whole-body glycolysis (both maximal and submaximal) sig
nificantly decreased by similar to 30% with 2 days of high-fat feeding
and remained suppressed thereafter (P < 0.05). Similar patterns of ch
anges in insulin-stimulated glucose uptake and glycolysis were also ob
served in skeletal muscle. Insulin-stimulated glycogen synthesis and g
lucose-6-phosphate (G-6-P) concentrations in skeletal muscle increased
significantly during the initial few days of high-fat feeding and gra
dually returned to control levels by day 14, suggesting that increased
G-6-P concentrations were responsible for increased glycogen synthesi
s. Thus, suppression of insulin-stimulated glycolysis and a compensato
ry increase in glycogen synthesis (presumably arising from the glucose
-fatty acid cycle) preceded decreases in insulin-stimulated glucose up
take in skeletal muscle during high-fat feeding. These findings sugges
t that the insulin resistance may develop as a secondary response to i
mpaired intracellular glucose metabolism.