Effects of individual fatty acids on glucose uptake and glycogen synthesis in soleus muscle in vitro.
Soleus muscle strips from Wistar rats were preincubated with palmitate in vitro before the determination of insulin-mediated glucose metabolism in fatty acid-free medium. Palmitate decreased insulin-stimulated glycogen synthesis to 51% of control in a time- (0-6 h) and concentration-dependent (0-2 mM) manner. Basal and insulin-stimulated glucose transport/phosphorylation also decreased with time, but the decrease occurred after the effect on glycogen synthesis. Preincubation with 1 mM palmitate, oleate, linoleate, or linolenate for 4 h impaired glycogen synthesis stimulated with a submaximal physiological insulin concentration (300 microU/ml) to 50-60% of the control response, and this reduction was associated with impaired insulin-stimulated phosphorylation of protein kinase B (PKB). Preincubation with different fatty acids (all 1 mM for 4 h) had varying effects on insulin-stimulated glucose transport/phosphorylation, which was decreased by oleate and linoleate, whereas palmitate and linolenate had little effect. Across groups, the rates of glucose transport/phosphorylation correlated with the intramuscular long-chain acyl-CoA content. The similar effects of individual fatty acids on glycogen synthesis but different effects on insulin-stimulated glucose transport/phosphorylation provide evidence that lipids may interact with these two pathways via different mechanisms.
Thompson
A L
AL
Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia. a.thompson@garvan.unsw.edu.au
Lim-Fraser
M Y
MY
Kraegen
E W
EW
Cooney
G J
GJ
D000214:Acyl Coenzyme A / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006003:Glycogen / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar
D000214:Acyl Coenzyme A; D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D011518:Proto-Oncogene Proteins; C015785:2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate; D000255:Adenosine Triphosphate; D006003:Glycogen; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose