TY - JOUR

T1 - Lipid induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling

AU - Høeg, Louise Dalgas

AU - Sjøberg, Kim Anker

AU - Jeppesen, Jacob

AU - Jensen, Thomas Elbenhardt

AU - Frøsig, Christian

AU - Birk, Jesper Bratz

AU - Bisiani, Bruno

AU - Hiscock, Natalie

AU - Pilegaard, Henriette

AU - Wojtaszewski, Jørgen

AU - Richter, Erik A.

AU - Kiens, Bente

N1 - CURIS 2011 5200 006

PY - 2011

Y1 - 2011

N2 - 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 and design 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 7h. Muscle biopsies were obtained before and during a euglycemic hyperinsulinemic (1.42 mU·kg(-1)·min(-1)) clamp. Results: Intralipid infusion reduced whole body glucose infusion rate 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. Conclusion: 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 glucose transporter activity. A higher leg lactate release and lower glucose oxidation with intralipid infusion may rather suggest a metabolic feed back regulation of glucose metabolism.

AB - 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 and design 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 7h. Muscle biopsies were obtained before and during a euglycemic hyperinsulinemic (1.42 mU·kg(-1)·min(-1)) clamp. Results: Intralipid infusion reduced whole body glucose infusion rate 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. Conclusion: 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 glucose transporter activity. A higher leg lactate release and lower glucose oxidation with intralipid infusion may rather suggest a metabolic feed back regulation of glucose metabolism.

U2 - 10.2337/db10-0698

DO - 10.2337/db10-0698

M3 - Journal article

C2 - 20956497

VL - 60

SP - 64

EP - 73

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 1

ER -