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

Abstract

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.

• Authors: Suraj Unniappan, Rhonda D Wideman, Christine Donald, Virginia Gunn, Jennifer L Wall, Qiu-Xia Zhang, Travis D Webber, Anthony T Cheung, Timothy J Kieffer
• Journal: Journal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 87 Issue 7 Pg. 703-12 (Jul 2009) ISSN: 1432-1440 [Electronic] Germany
• PMID: 19387601 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hormone Antagonists
• Insulin
• Mifepristone

Topics

• Animals
• Cell Line, Tumor (transplantation)
• Cell- and Tissue-Based Therapy (methods)
• Diabetes Mellitus, Experimental (therapy)
• Gene Expression Regulation (drug effects)
• Hormone Antagonists (pharmacology)
• Humans
• Insulin (metabolism)
• Intestinal Mucosa (metabolism)
• Intestines (cytology)
• Male
• Mice
• Mice, Inbred BALB C
• Mifepristone (pharmacology)
• Time Factors