title: Insulin-expressing engineered cell lines and primary cells: surrogate β cells from liver, gut, and other sources.
abstract: OBJECTIVE
  Islet transplantation is being used to treat type 1 diabetes but is currently limited by the shortage of tissue available and by insufficient long-term function of transplanted islets. Thus, there remains significant interest in developing substitute sources of insulin-producing cells. Here we review progress in this area, focusing on insulin gene therapy and generation of new insulin-producing cells by redirecting hepatic and intestinal tissues towards a β-cell phenotype.
  
  
  RESULTS
  Insulin gene therapy using non-β cells has been improved by utilizing modified insulin constructs controlled by regulatory elements to confer nutrient responsiveness, and by inducing insulin production in endocrine cells that are equipped for rapid and in some cases glucose-responsive secretion. Significant advances have also been made towards generation of insulin-producing cells via transcriptional manipulation of hepatic and intestinal cells. These approaches offer the potential of generating a virtually limitless supply of insulin-producing cells.
  
  
  CONCLUSIONS
  The major challenge associated with insulin gene therapy in non-β cells is to achieve rapid, glucose-responsive secretion, while transdifferentiation approaches require additional characterization of the function and stability of insulin-producing cells. Continued efforts in these areas are warranted, as re-establishment of endogenous insulin production would be a welcome replacement to insulin injections for diabetes treatment.
authors: aLaboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, CanadabDepartment of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Rhonda D
authors: RD
authors: Wideman
authors: Yukihiro
authors: Y
authors: Fujita
authors: Timothy J
authors: TJ
authors: Kieffer