title: Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: Stanley Ck
authors.initials: SC
authors.lastname: Cheung
authors.forename: Li-Zhong
authors.initials: LZ
authors.lastname: Liu
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Lan
authors.forename: Qiao-Quan
authors.initials: QQ
authors.lastname: Liu
authors.forename: Samuel Sm
authors.initials: SS
authors.lastname: Sun
authors.forename: Juliana Cn
authors.initials: JC
authors.lastname: Chan
authors.forename: Peter Cy
authors.initials: PC
authors.lastname: Tong
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D018506:Gene Expression Regulation, Plant; D005983:Glutens / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009842:Oligopeptides; D012275:Oryza / Q000737:chemistry / Q000235:genetics*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D030821:Plants, Genetically Modified / Q000737:chemistry / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D021382:Protein Sorting Signals; D051381:Rats; D011924:Rats, Zucker; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D012639:Seeds / Q000737:chemistry / Q000235:genetics; D013213:Starch / Q000032:analysis; D014170:Transformation, Genetic
chemical_list: D001786:Blood Glucose; D018076:DNA, Complementary; D009842:Oligopeptides; D010936:Plant Extracts; D021382:Protein Sorting Signals; D011994:Recombinant Proteins; C073762:lysyl-aspartyl-glutamyl-leucine; D007334:Insulin-Like Growth Factor I; D005983:Glutens; D013213:Starch