Treatment of diabetes by transplantation of drug-inducible insulin-producing gut cells

被引:12
|
作者
Unniappan, Suraj [1 ]
Wideman, Rhonda D. [1 ]
Donald, Christine [1 ]
Gunn, Virginia [1 ]
Wall, Jennifer L. [1 ]
Zhang, Qiu-Xia [2 ]
Webber, Travis D. [1 ]
Cheung, Anthony T. [3 ]
Kieffer, Timothy J. [1 ]
机构
[1] Univ British Columbia, Dept Cellular & Physiol Sci, Lab Mol & Cellular Med, Vancouver, BC V6T 1Z3, Canada
[2] Univ Alberta, Dept Med, Edmonton, AB T6G 2R7, Canada
[3] EnGene Inc, Vancouver, BC V6T 1Z3, Canada
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 2009年 / 87卷 / 07期
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
Diabetes; Transplantation; Insulin; Cell therapy; Inducible; K-cell; GASTRIC-INHIBITORY POLYPEPTIDE; EMBRYONIC STEM-CELLS; ISLET TRANSPLANTATION; GENE-THERAPY; GLUCOSE; RATS; MICE; HEPATOCYTES; SECRETION; REVERSAL;
D O I
10.1007/s00109-009-0465-0
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Most patients with type 1 diabetes rely on multiple daily insulin injections to maintain blood glucose control. However, insulin injections carry the risk of inducing hypoglycemia and do not eliminate diabetic complications. We sought to develop and evaluate a regulatable cell-based system for delivery of insulin to treat diabetes. We generated two intestinal cell lines in which human insulin expression is controlled by mifepristone. Insulin mRNA expression was dependent on the mifepristone dose and incubation time and cells displayed insulin and C-peptide immunoreactivity and glucose-induced insulin release following mifepristone treatment. Cell transplantation followed by mifepristone administration reversed streptozotocin (STZ)-induced diabetes in mice, and this effect was dependent on the mifepristone dose delivered. These data support the notion that engineering regulatable insulin expression within a cell already equipped for regulated secretion may be efficacious for the treatment of insulin-dependent diabetes.
引用
收藏
页码:703 / 712
页数:10
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