Lipid-induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling.
OBJECTIVE
We have previously shown that overnight fasted women have higher insulin-stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism than men. We therefore hypothesized that women would be less prone to lipid-induced insulin resistance.


METHODS
Insulin sensitivity of whole-body and leg glucose disposal was studied in 16 young well-matched healthy men and women infused with intralipid or saline for 7 h. Muscle biopsies were obtained before and during a euglycemic-hyperinsulinemic clamp (1.42 mU · kg⁻¹ · min⁻¹).


RESULTS
Intralipid infusion reduced whole-body glucose infusion rate by 26% in women and 38% in men (P < 0.05), and insulin-stimulated leg glucose uptake was reduced significantly less in women (45%) than men (60%) after intralipid infusion. Hepatic glucose production was decreased during the clamp similarly in women and men irrespective of intralipid infusion. Intralipid did not impair insulin or AMPK signaling in muscle and subcutaneous fat, did not cause accumulation of muscle lipid intermediates, and did not impair insulin-stimulated glycogen synthase activity in muscle or increase plasma concentrations of inflammatory cytokines. In vitro glucose transport in giant sarcolemmal vesicles was not decreased by acute exposure to fatty acids. Leg lactate release was increased and respiratory exchange ratio was decreased by intralipid.


CONCLUSIONS
Intralipid infusion causes less insulin resistance of muscle glucose uptake in women than in men. This insulin resistance is not due to decreased canonical insulin signaling, accumulation of lipid intermediates, inflammation, or direct inhibition of GLUT activity. Rather, a higher leg lactate release and lower glucose oxidation with intralipid infusion may suggest a metabolic feedback regulation of glucose metabolism.
Copenhagen Muscle Research Centre, Department of Exercise and Sport Sciences, University of Copenhagen, Denmark.
Louise D
LD
Høeg
Kim A
KA
Sjøberg
Jacob
J
Jeppesen
Thomas E
TE
Jensen
Christian
C
Frøsig
Jesper B
JB
Birk
Bruno
B
Bisiani
Natalie
N
Hiscock
Henriette
H
Pilegaard
Jørgen F P
JF
Wojtaszewski
Erik A
EA
Richter
Bente
B
Kiens
D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D000818:Animals; D001481:Basal Metabolism / Q000502:physiology; D001783:Blood Flow Velocity; D001827:Body Height; D015992:Body Mass Index; D004655:Emulsions / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D004958:Estradiol / Q000097:blood; D015444:Exercise; D005215:Fasting; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007249:Inflammation / Q000503:physiopathology / Q000517:prevention & control; D007328:Insulin / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption; D010743:Phospholipids / Q000494:pharmacology*; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction / Q000502:physiology*; D013024:Soybean Oil / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
D052242:Adiponectin; D004655:Emulsions; D007328:Insulin; D008055:Lipids; D010743:Phospholipids; D014280:Triglycerides; C545823:soybean oil, phospholipid emulsion; D004958:Estradiol; D013024:Soybean Oil; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine