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PMID: 20616080 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic beta-like cells.

Alipio Z, Liao W, Roemer EJ, Waner M, Fink LM, Ward DC, Ma Y

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.

MeSH Terms
Animals Blood Glucose/analysis Cell Differentiation Cell Transplantation/methods Cells, Cultured Diabetes Mellitus, Type 1/complications,surgery Diabetes Mellitus, Type 2/complications,surgery Disease Models, Animal Fluorescent Antibody Technique Glycated Hemoglobin A/analysis Green Fluorescent Proteins/genetics,metabolism Humans Hyperglycemia/blood,complications,prevention & control Induced Pluripotent Stem Cells/cytology,metabolism,transplantation Insulin/analysis,metabolism Insulin Secretion Insulin-Secreting Cells/cytology,metabolism,transplantation Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Nude Mice, Transgenic
Chemicals
Blood Glucose Glycated Hemoglobin A Insulin Green Fluorescent Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Alipio Zaida
Division of Laboratory Medicine, Nevada Cancer Institute, Las Vegas, NV 89135, USA.
Liao Wenbin
Roemer Elizabeth J
Waner Milton
Fink Louis M
Ward David C
Ma Yupo
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
Published
2010-07-27
Epub
2010-00-07
Pages
13426-31
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2922145
Subset
IM
Grants
NHLBI NIH HHS · R01 HL087948 · United States
NHLBI NIH HHS · R01HL087948 · United States
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