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

BACKGROUND: Human 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. I...

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Autores principales: Cheung, Stanley CK, Liu, Li-zhong, Lan, Lin-lin, Liu, Qiao-quan, Sun, Samuel SM, Chan, Juliana CN, Tong, Peter CY
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098155/
https://www.ncbi.nlm.nih.gov/pubmed/21486461
http://dx.doi.org/10.1186/1472-6750-11-37
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author Cheung, Stanley CK
Liu, Li-zhong
Lan, Lin-lin
Liu, Qiao-quan
Sun, Samuel SM
Chan, Juliana CN
Tong, Peter CY
author_facet Cheung, Stanley CK
Liu, Li-zhong
Lan, Lin-lin
Liu, Qiao-quan
Sun, Samuel SM
Chan, Juliana CN
Tong, Peter CY
author_sort Cheung, Stanley CK
collection PubMed
description BACKGROUND: Human 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. RESULTS: The 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. CONCLUSION: Our 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.
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spelling pubmed-30981552011-05-20 Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies Cheung, Stanley CK Liu, Li-zhong Lan, Lin-lin Liu, Qiao-quan Sun, Samuel SM Chan, Juliana CN Tong, Peter CY BMC Biotechnol Research Article BACKGROUND: Human 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. RESULTS: The 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. CONCLUSION: Our 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. BioMed Central 2011-04-12 /pmc/articles/PMC3098155/ /pubmed/21486461 http://dx.doi.org/10.1186/1472-6750-11-37 Text en Copyright ©2011 Cheung et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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.
spellingShingle Research Article
Cheung, Stanley CK
Liu, Li-zhong
Lan, Lin-lin
Liu, Qiao-quan
Sun, Samuel SM
Chan, Juliana CN
Tong, Peter CY
Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies
title Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies
title_full Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies
title_fullStr Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies
title_full_unstemmed Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies
title_short Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies
title_sort glucose lowering effect of transgenic human insulin-like growth factor-i from rice: in vitro and in vivo studies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098155/
https://www.ncbi.nlm.nih.gov/pubmed/21486461
http://dx.doi.org/10.1186/1472-6750-11-37
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