title: 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.affiliation: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Suraj
authors.initials: S
authors.lastname: Unniappan
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Wideman
authors.forename: Christine
authors.initials: C
authors.lastname: Donald
authors.forename: Virginia
authors.initials: V
authors.lastname: Gunn
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Wall
authors.forename: Qiu-Xia
authors.initials: QX
authors.lastname: Zhang
authors.forename: Travis D
authors.initials: TD
authors.lastname: Webber
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Cheung
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kieffer
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor / Q000637:transplantation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D006727:Hormone Antagonists; D007328:Insulin; D015735:Mifepristone