title: Challenges for gene therapy of type 1 diabetes.
abstract: Type 1 or insulin-dependent diabetes mellitus is caused by autoimmune attack and selective destruction of the pancreatic beta cells. Despite the development of various insulin replacement therapies, insulin injection still remains the mainstay treatment for type 1 diabetes. However, exogenous insulin administration cannot achieve the same degree of glycemic control as provided by endogenous insulin produced from the pancreatic beta cells. Insulin gene transfer is being developed to improve the quality of glycemic control by restoring endogenous insulin production in type 1 diabetes. Nevertheless, attempts to achieve adequately regulated insulin production are stymied by the lack of appropriate surrogate cells that are able to detect blood glucose variations and release insulin in a glucose-dependent manner. Although limited success has been made to control insulin gene expression in ectopic cells using hormone/glucose-regulated expression systems, these transcriptionally regulated systems are relatively slow in the "on-" and "off"-kinetics of insulin production, raising a serious safety concern for clinical application. In this article, we will review recent advances made to address this concern and highlight the importance of insulin gene transfer to cell types that possess an intrinsic ability to kinetically mimic the pancreatic beta cells in terms of glucose-responsive insulin secretion.
authors.affiliation: Carl Icahn Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. hengjiang.dong@mssm.edu
authors.forename: H
authors.initials: H
authors.lastname: Dong
authors.forename: K
authors.initials: K
authors.lastname: Anthony
authors.forename: N
authors.initials: N
authors.lastname: Morral
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D015316:Genetic Therapy; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D007328:Insulin / Q000096:biosynthesis
chemical_list: D001786:Blood Glucose; D007328:Insulin