title: Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic beta-like cells.
abstract: Diabetes mellitus is characterized by either the inability to produce insulin (type 1 diabetes) or as insensitivity to insulin secreted by the body (type 2 diabetes). In either case, the body is unable to move blood glucose efficiently across cell membranes to be used. This leads to a variety of local and systemic detrimental effects. Current treatments for diabetes focus on exogenous insulin administration and dietary control. Here, we describe a potential cure for diabetes using a cellular therapy to ameliorate symptoms associated with both reduced insulin secretion and insulin sensitivity. Using induced pluripotent stem (iPS) cells, we were able to derive beta-like cells similar to the endogenous insulin-secreting cells in mice. These beta-like cells secreted insulin in response to glucose and corrected a hyperglycemic phenotype in two mouse models of type 1 and 2 diabetes via an iPS cell transplant. Long-term correction of hyperglycemia was achieved, as determined by blood glucose and hemoglobin A1c levels. These data provide an initial proof of principle for potential clinical applications of reprogrammed somatic cells in the treatment of diabetes type 1 or 2.
authors.affiliation: Division of Laboratory Medicine, Nevada Cancer Institute, Las Vegas, NV 89135, USA.
authors.forename: Zaida
authors.initials: Z
authors.lastname: Alipio
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liao
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Roemer
authors.forename: Milton
authors.initials: M
authors.lastname: Waner
authors.forename: Louis M
authors.initials: LM
authors.lastname: Fink
authors.forename: David C
authors.initials: DC
authors.lastname: Ward
authors.forename: Yupo
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002454:Cell Differentiation; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000601:surgery*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000601:surgery*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D008822:Mice, Transgenic
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D049452:Green Fluorescent Proteins; D007328:Insulin