Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivostudies

BMC Biotechnology

Research Article

Qiao-quan Liu¹  Stanley CK Cheung²  Juliana CN Chan²  Peter CY Tong²  Li-zhong Liu²  Lin-lin Lan²  Samuel SM Sun² 

[1] Department of Biology, The Chinese University of Hong Kong, Shatin, Hong Kong;Key Laboratory of Plant Functional Genomics of the Ministry of Education, Agricultural College, Yangzhou University, 225009, Jiangsu, PR China;Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;

关键词: Oryza sativa L., plant bioreactor;    transgenic plant;    recombinant protein;    protein targeting;    KDEL;    IGF-I;   

DOI  :  10.1186/1472-6750-11-37

 received in 2010-07-07, accepted in 2011-04-12,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundHuman insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains.ResultsThe plant-codon-optimized hIGF-I was introduced into rice via Agrobacterium-mediated transformation. To enhance the stability and yield of rhIGF-I, the endoplasmic reticulum-retention signal and glutelin signal peptide were used to deliver rhIGF-I to endoplasmic reticulum for stable accumulation. We found that only glutelin signal peptide could lead to successful expression of hIGF-I and one gram of hIGF-I rice grain possessed the maximum activity level equivalent to 3.2 micro molar of commercial rhIGF-I. In vitro functional analysis showed that the rice-derived rhIGF-I was effective in inducing membrane ruffling and glucose uptake on rat skeletal muscle cells. Oral meal test with rice-containing rhIGF-I acutely reduced blood glucose levels in streptozotocin-induced and Zucker diabetic rats, whereas it had no effect in normal rats.ConclusionOur findings provided an alternative expression system to produce large quantities of biologically active rhIGF-I. The provision of large quantity of recombinant proteins will promote further research on the therapeutic potential of rhIGF-I.

【 授权许可】

Unknown   
© Cheung et al; licensee BioMed Central Ltd. 2011. 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/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.