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World J Gastroenterol. Jul 14, 2008; 14(26): 4209-4215
Published online Jul 14, 2008. doi: 10.3748/wjg.14.4209
Gene therapy for type 1 diabetes mellitus in rats by gastrointestinal administration of chitosan nanoparticles containing human insulin gene
Li Niu, Yan-Cheng Xu, Zhe Dai, Hui-Qin Tang
Li Niu, Yan-Cheng Xu, Zhe Dai, Hui-Qin Tang, Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
Author contributions: Niu L and Xu YC contributed equally to this work; Niu L and Xu YC designed the research; Niu L performed the research; Dai Z and Tang HQ contributed to new reagents/analytic tools; Niu L, Xu YC, Dai Z and Tang HQ analyzed the data; Niu L and Xu YC wrote the paper.
Correspondence to: Yan-Cheng Xu, Professor, Department of Endocrinology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, Hubei Province, China. endocrine@mail.whu.edu.cn
Telephone: +86-27-62605165
Fax: +86-27-67812892
Received: May 1, 2008
Revised: June 2, 2008
Accepted: June 9, 2008
Published online: July 14, 2008
Abstract

AIM: To study the expression of human insulin gene in gastrointestinal tracts of diabetic rats.

METHODS: pCMV.Ins, an expression plasmid of the human insulin gene, wrapped with chitosan nanoparticles, was transfected to the diabetic rats through lavage and coloclysis, respectively. Fasting blood glucose and plasma insulin levels were measured for 7 d. Reverse transcription polymerase chain reaction (RT-PCR) analysis and Western blot analysis were performed to confirm the expression of human insulin gene.

RESULTS: Compared with the control group, the fasting blood glucose levels in the lavage and coloclysis groups were decreased significantly in 4 d (5.63 ± 0.48 mmol/L and 5.07 ± 0.37 mmol/L vs 22.12 ± 1.31 mmol/L, respectively, P < 0.01), while the plasma insulin levels were much higher (32.26 ± 1.81 &mgr;IU/mL and 32.79 ± 1.84 &mgr;IU/mL vs 14.23 ± 1.38 &mgr;IU/mL, respectively, P < 0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and coloclysis groups.

CONCLUSION: Human insulin gene wrapped with chitosan nanoparticles can be successfully transfected to rats through gastrointestinal tract, indicating that chitosan is a promising non-viral vector.

Keywords: Gastrointestinal tract; Human insulin gene; Gene expression; Diabetes mellitus; Chitosan nanoparticle