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Lipid-induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling.

Høeg LD, Sjøberg KA, Jeppesen J, Jensen TE, Frøsig C, Birk JB, Bisiani B, Hiscock N, Pilegaard H, Wojtaszewski JF, Richter EA, Kiens B - Diabetes (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Copenhagen Muscle Research Centre, Department of Exercise and Sport Sciences, University of Copenhagen, Denmark.

ABSTRACT

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.

Research design and 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.

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Glucose infusion rate and insulin-stimulated leg glucose uptake in women and men in the control (□) and intralipid (■) trial. A: Glucose infusion rate the last 30 min of the clamp. B: Delta glucose infusion rate the last 120 min of the clamp, expressed as the difference between the control and the intralipid trial. C: Insulin-stimulated leg glucose uptake during the 120-min clamp in the control trial. D: Insulin-stimulated leg glucose uptake during the 120-min clamp in the intralipid trial. E: Insulin-stimulated leg glucose uptake the last 30 min of the clamp. F: Delta insulin-stimulated leg glucose uptake the last 30 min of the clamp expressed as the difference between the control and the intralipid trial. *P < 0.05 vs. control trial, #P < 0.05 vs. women. Data are means ± SE; n = 16.
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Figure 1: Glucose infusion rate and insulin-stimulated leg glucose uptake in women and men in the control (□) and intralipid (■) trial. A: Glucose infusion rate the last 30 min of the clamp. B: Delta glucose infusion rate the last 120 min of the clamp, expressed as the difference between the control and the intralipid trial. C: Insulin-stimulated leg glucose uptake during the 120-min clamp in the control trial. D: Insulin-stimulated leg glucose uptake during the 120-min clamp in the intralipid trial. E: Insulin-stimulated leg glucose uptake the last 30 min of the clamp. F: Delta insulin-stimulated leg glucose uptake the last 30 min of the clamp expressed as the difference between the control and the intralipid trial. *P < 0.05 vs. control trial, #P < 0.05 vs. women. Data are means ± SE; n = 16.

Mentions: In the control trial, insulin-stimulated whole-body glucose infusion rate to maintain euglycemia was 54 ± 5 and 56 ± 5 μmol · min−1 · kg−1 LBM in women and men, respectively (Fig. 1A). Glucose infusion rate was decreased (P < 0.05) by intralipid infusion and significantly more in men (−38%) than in women (−24%) also when expressed in absolute numbers (Fig. 1B).


Lipid-induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling.

Høeg LD, Sjøberg KA, Jeppesen J, Jensen TE, Frøsig C, Birk JB, Bisiani B, Hiscock N, Pilegaard H, Wojtaszewski JF, Richter EA, Kiens B - Diabetes (2010)

Glucose infusion rate and insulin-stimulated leg glucose uptake in women and men in the control (□) and intralipid (■) trial. A: Glucose infusion rate the last 30 min of the clamp. B: Delta glucose infusion rate the last 120 min of the clamp, expressed as the difference between the control and the intralipid trial. C: Insulin-stimulated leg glucose uptake during the 120-min clamp in the control trial. D: Insulin-stimulated leg glucose uptake during the 120-min clamp in the intralipid trial. E: Insulin-stimulated leg glucose uptake the last 30 min of the clamp. F: Delta insulin-stimulated leg glucose uptake the last 30 min of the clamp expressed as the difference between the control and the intralipid trial. *P < 0.05 vs. control trial, #P < 0.05 vs. women. Data are means ± SE; n = 16.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3012198&req=5

Figure 1: Glucose infusion rate and insulin-stimulated leg glucose uptake in women and men in the control (□) and intralipid (■) trial. A: Glucose infusion rate the last 30 min of the clamp. B: Delta glucose infusion rate the last 120 min of the clamp, expressed as the difference between the control and the intralipid trial. C: Insulin-stimulated leg glucose uptake during the 120-min clamp in the control trial. D: Insulin-stimulated leg glucose uptake during the 120-min clamp in the intralipid trial. E: Insulin-stimulated leg glucose uptake the last 30 min of the clamp. F: Delta insulin-stimulated leg glucose uptake the last 30 min of the clamp expressed as the difference between the control and the intralipid trial. *P < 0.05 vs. control trial, #P < 0.05 vs. women. Data are means ± SE; n = 16.
Mentions: In the control trial, insulin-stimulated whole-body glucose infusion rate to maintain euglycemia was 54 ± 5 and 56 ± 5 μmol · min−1 · kg−1 LBM in women and men, respectively (Fig. 1A). Glucose infusion rate was decreased (P < 0.05) by intralipid infusion and significantly more in men (−38%) than in women (−24%) also when expressed in absolute numbers (Fig. 1B).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Copenhagen Muscle Research Centre, Department of Exercise and Sport Sciences, University of Copenhagen, Denmark.

ABSTRACT

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.

Research design and 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.

Show MeSH
Related in: MedlinePlus