title: Engineering the gut for insulin replacement to treat diabetes.
abstract: The gut epithelium's large surface area, its direct exposure to ingested nutrients, its vast stem cell population and its immunotolerogenic environment make it an excellent candidate for therapeutic cells to treat diabetes. Thus, several attempts have been made to coax immature gut cells to differentiate into insulin-producing cells by altering the expression patterns of specific transcription factors. Furthermore, because of similarities in enteroendocrine and pancreatic endocrine cell differentiation pathways, other approaches have used genetically engineered enteroendocrine cells to produce insulin in addition to their endogenous secreted hormones. Several studies support the utility of both of these approaches for the treatment of diabetes. Converting a patient's own gut cells into meal-regulated insulin factories in a safe and immunotolerogenic environment is an attractive approach to treat and potentially cure diabetes. Here, we review work on these approaches and indicate where we feel further advancements are required.
authors.affiliation: Laboratory of Molecular and Cellular Medicine Department of Cellular and Physiological Sciences Life Sciences Institute University of British Columbia Vancouver British Columbia Canada.
authors.forename: Majid
authors.initials: M
authors.lastname: Mojibian
authors.affiliation: Laboratory of Molecular and Cellular Medicine Department of Cellular and Physiological Sciences Life Sciences Institute University of British Columbia Vancouver British Columbia Canada.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Glavas
authors.affiliation: Laboratory of Molecular and Cellular Medicine Department of Cellular and Physiological Sciences Life Sciences Institute University of British Columbia Vancouver British Columbia Canada.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kieffer
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D060846:Cell Engineering; D003920:Diabetes Mellitus / Q000628:therapy*; D019858:Enteroendocrine Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D051381:Rats; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*
chemical_list: D007328:Insulin
keywords: Cell differentiation; Enterocytes; Enteroendocrine cells