Leucine supplementation in rats induced a delay in muscle IR/PI3K signaling pathway associated with overall impaired glucose tolerance

被引:46
作者
Balage, Michele [1 ,2 ,3 ]
Dupont, Joelle [4 ]
Mothe-Satney, Isabelle [5 ,6 ]
Tesseraud, Sophie [7 ]
Mosoni, Laurent [2 ,3 ]
Dardevet, Dominique [2 ,3 ]
机构
[1] INRA, UNH Ctr Clermont Ferrand Theix, UMR Nutr Humaine 1019, F-63122 St Genes Champanelle, France
[2] Clermont Univ, UFR Med, UMR Nutr Humaine 1019, F-63000 Clermont Ferrand, France
[3] CRNH Auvergne, F-63000 Clermont Ferrand, France
[4] INRA, UMR Physiol Reprod & Comportements 85, F-37380 Nouzilly, France
[5] INSERM U907, F-06000 Nice, France
[6] Univ Nice Sophia Antipolis, Fac Med, F-06107 Nice, France
[7] INRA, Rech Avicoles UR83, F-37380 Nouzilly, France
关键词
Leucine; Insulin; Signaling; Glucose tolerance; Rat; INDUCED INSULIN-RESISTANCE; DIET-INDUCED OBESITY; LOWERING AMINO-ACID; SKELETAL-MUSCLE; PROTEIN-SYNTHESIS; OLD RATS; CO-INGESTION; MAMMALIAN TARGET; ADIPOSE-TISSUE; ISOLEUCINE;
D O I
10.1016/j.jnutbio.2010.02.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although activation of the mammalian target of rapamycin complex/p70 S6 kinase (S6K1) pathway by leucine is efficient to stimulate muscle protein synthesis, it can also exert inhibition on the early steps of insulin signaling leading to insulin resistance. We investigated the impact of 5-week leucine supplementation on insulin signaling and sensitivity in 4-month old rats fed a 15% protein diet supplemented (LEU) or not (C) with 4.5% leucine. An oral glucose tolerance test was performed in each rat at the end of the supplementation and glucose transport was measured in vitro using isolated epitrochlearis muscles incubated with 2-deoxy-D-[H-3]-glucose under increasing insulin concentrations. Insulin signaling was assessed on gastrocnemius at the postabsorptive state or 30 and 60 min after gavage with a nutrient bolus. Tyrosine phosphorylation of IR beta, IRS1 and PI3 kinase activity were reduced in LEU group 30 min after feeding (-36%, -36% and -38% respectively, P<.05) whereas 56K1, S6rp and 4EBP1 phosphorylations were similar. Overall glucose tolerance was reduced in leucine-supplemented rats and was associated with accumulation of perirenal adipose tissue (+27%, P<.05). Conversely, in vitro insulin-response of muscle glucose transport tended to be improved in leucine-supplemented rats. In conclusion, dietary leucine supplementation in adult rats induced a delay in the postprandial stimulation in the early steps of muscle insulin signaling without muscle resistance on insulin-induced glucose uptake. However, it resulted in overall glucose intolerance linked to increased local adiposity. Further investigations are necessary to clearly define the beneficial and/or deleterious effects of chronic dietary leucine supplementation in healthy subjects. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:219 / 226
页数:8
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