L-Citrulline increases hepatic sensitivity to insulin by reducing the phosphorylation of serine 1101 in insulin receptor substrate-1

BMC Complementary and Alternative Medicine

Research Article

Yewei Huang¹  Xiao Ma²  Yoshie Yamagishi³  Shiori Suguro³  Maki Momoo⁴  Hisae Yoshitomi⁴  Ming Gao⁴ 

[1] College of Life Science, Jilin University, 130012, Changchun, China;Key Laboratory of Pu-erh Tea Science, Yunnan Agricultural University, 650201, Kunming, China;Protein Chemical Co., LTD, 1000011, Tokyo, Japan;School of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Koshien Kyuban-cho, 663-8179, Nishinomiya, Hyogo, Japan;

关键词: Insulin resistance;    L-citrulline;    Insulin receptor substrate-1;    SHRSP.Z-Leprfa/IzmDmcr rat;    H4IIE cells;   

DOI  :  10.1186/s12906-015-0706-4

 received in 2014-10-28, accepted in 2015-06-01,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundInsulin resistance is characterized by deficient responses to insulin in its target tissues. In the present study, we examined the effects of L-Citrulline (L-Cit) on insulin sensitivity and signaling cascades in rat hepatoma H4IIE cells and SHRSP.Z-Leprfa/IzmDmcr rats.MethodsH4IIE cells were pretreated in the presence or absence of 250 μM L-Cit in serum-free medium and then incubated in the presence or absence of 0.1 nM insulin. Rats were allocated into 2 groups; a control group (not treated) and L-Cit group (2 g/kg/day, L-Cit) and treated for 8 weeks.ResultsL-Cit enhanced the insulin-induced phosphorylation of Akt in H4IIE cells. Moreover, the inhibited expression of Dex/cAMP-induced PEPCK mRNA by insulin was enhanced by the L-Cit treatment. The phosphorylation of tyrosine, which is upstream of Akt, in insulin receptor substrate-1 (IRS-1) was increased by the L-Cit treatment. The L-Cit-induced enhancement in insulin signaling was not related to the binding affinity of insulin to the insulin receptor or to the expression of the insulin receptor, but to a decrease in the phosphorylation of serine 1101 in IRS-1. These results were also confirmed in animal experiments. In the livers of L-Cit-treated rats, PI3K/Akt signaling was improved by decreases in the phosphorylation of serine 1101.ConclusionsWe herein demonstrated for the first time the beneficial effects of L-Cit on improved insulin resistance associated with enhanced insulin sensitivity. These results may have clinical applications for insulin resistance and the treatment of type-2 diabetes.

【 授权许可】

Unknown   
© Yoshitomi et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.