Jk. Kim et al., PLASMA-FREE FATTY-ACIDS DECREASE INSULIN-STIMULATED SKELETAL-MUSCLE GLUCOSE-UPTAKE BY SUPPRESSING GLYCOLYSIS IN CONSCIOUS RATS, Diabetes, 45(4), 1996, pp. 446-453
Citations number
39
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
The effects of elevated plasma free fatty acid (FFA) levels on insulin
-stimulated whole-body and skeletal muscle glucose transport, glucose
uptake, glycolysis, and glycogen synthesis were studied in conscious r
ats during hyperinsulinemic-euglycemic clamps with (n = 26) or without
(n = 23) Intralipid and heparin infusion. Whole-body and skeletal mus
cle glucose uptake, glycolysis, and glycogen synthesis were estimated
using D-[3-H-3]glucose and 2-[C-14]deoxyglucose (study 1), and glucose
transport activity was assessed by analyzing plasma kinetics of L-[C-
14]glucose and 3-O-[H-3]-methylglucose (study 2). Plasma FFA levels de
creased during the clamps without intralipid but increased above basal
during the clamps with Intralipid infusion (P < 0.01 for both). Eleva
ted plasma FFA levels decreased insulin-stimulated whole-body glucose
uptake by similar to 15% and similar to 20% during physiological and m
aximal insulin clamps, respectively (P < 0.01). Similarly, insulin-sti
mulated glucose uptake was also decreased in individual skeletal muscl
es with Intralipid infusion (P < 0.05). The most profound effect of el
evated plasma FFA levels was a 30-50% suppression of insulin-stimulate
d glycolysis in whole body and individual skeletal muscles in both cla
mps. In contrast, physiological insulin-stimulated glycogen synthesis
was increased with elevated plasma. FFA levels in whole body and indiv
idual skeletal muscles (P < 0.05). Glucose-6-phosphate (G-6-P) levels
were increased in soleus and extensors digitorum longus (EDL) muscles
with Intralipid infusion in both clamps (P < 0.05). Intralipid infusio
n did not alter the time profiles of plasma L-glucose and 3-O-methylgl
ucose after an intravenous injection during maximal insulin clamps, an
d compartmental analysis indicated no significant effect of elevated F
FA levels on glucose transport activity in insulin-sensitive tissues (
P > 0.05). Thus, elevated plasma FFA decreased insulin-stimulated gluc
ose uptake in skeletal muscle by suppressing glycolysis and increasing
G-6-P levels. These findings suggest that the classic glucose-fatty a
cid cycle was the predominant mechanism underlying the inhibitory effe
ct of FFA on skeletal muscle glucose uptake.