A biologically active rhIGF-1 fusion accumulated in transgenic rice seeds can reduce blood glucose in diabetic mice via oral delivery.
Human insulin-like growth factor 1(hIGF-1) is essential for cell proliferation and used therapeutically in treating various diseases including diabetes mellitus. Here, we present that a recombinant hIGF-1(rhIGF-1) was expressed fused with the C-terminus of a rice luminal binding protein and accumulated highly in rice seeds, reaching 6.8+/-0.5% of total seed protein. The rhIGF-1 fusion was demonstrated to possess biological activity to stimulate cell proliferation. Importantly, the unprocessed transgenic seeds could significantly increase plasma rhIGF-1 level and reduce blood glucose of diabetic mice via oral delivery. Further studies suggested that transgenic seeds reduced blood glucose of diabetic mice by enhancing islet cells survival and increasing insulin secretion rather than increasing insulin sensitivity. These results indicated the potential of the novel fusion expression system in production and oral delivery of biologically active small peptides for diseases.
Xie
Tingting
T
Center of Engineering and Research of the Ministry of Education for Plant Biotechnology and Germplasm Utilization, Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
Qiu
Qingchuan
Q
Zhang
Wei
W
Ning
Tingting
T
Yang
Wei
W
Zheng
Congyi
C
Wang
Chuan
C
Zhu
Yingguo
Y
Yang
Daichang
D
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D012275:Oryza / Q000235:genetics; D030821:Plants, Genetically Modified; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D012639:Seeds / Q000235:genetics*; D014407:Tumor Cells, Cultured
D001786:Blood Glucose; D011993:Recombinant Fusion Proteins; D007334:Insulin-Like Growth Factor I