Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes

Type 1 diabetes mellitus (T1DM) is an autoimmune disease leading to near complete pancreatic β-cell destruction. New evidence suggests that β-cell regeneration is possible, but ongoing autoimmune damage prevents restoration of β-cell mass. We tested the hypothesis that simultaneously blocking autoim...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2006-06, Vol.344 (3), p.1017-1022
Main Authors: Yang, Zandong, Chen, Meng, Carter, Jeffrey D., Nunemaker, Craig S., Garmey, James C., Kimble, Sarah D., Nadler, Jerry L.
Format: Article
Language:English
Subjects:
Animals
Autoimmunity
BIOLOGICAL RECOVERY
CELL PROLIFERATION
COMBINED THERAPY
Cytokine
DAMAGE
DIABETES MELLITUS
Diabetes Mellitus, Type 1 - drug therapy
Diabetes Mellitus, Type 1 - immunology
Diabetes Mellitus, Type 1 - pathology
Drug Combinations
Exendin-4
INFLAMMATION
INSULIN
Insulin-Secreting Cells - drug effects
Insulin-Secreting Cells - immunology
Islet
Lisofylline
MICE
Mice, Inbred C57BL
Non-obese diabetic (NOD) mice
PANCREAS
Pentoxifylline - administration & dosage
Pentoxifylline - analogs & derivatives
Peptides - administration & dosage
Proliferation
RADIOLOGY AND NUCLEAR MEDICINE
Treatment Outcome
Type 1 diabetes
Venoms - administration & dosage
β-Cell neogenesis
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Summary:Type 1 diabetes mellitus (T1DM) is an autoimmune disease leading to near complete pancreatic β-cell destruction. New evidence suggests that β-cell regeneration is possible, but ongoing autoimmune damage prevents restoration of β-cell mass. We tested the hypothesis that simultaneously blocking autoimmune cytokine damage and supplying a growth-promoting stimulus for β-cells would provide a novel approach to reverse T1DM. Therefore, in this study we combined lisofylline to suppress autoimmunity and exendin-4 to enhance β-cell proliferation for treating autoimmune-mediated diabetes in the non-obese diabetic (NOD) mouse model. We found that this combined therapy effectively reversed new-onset diabetes within a week of therapy, and even maintained euglycemia up to 145 days after treatment withdrawal. The therapeutic effect of this regimen was associated with improved β-cell metabolism and insulin secretion, while reducing β-cell apoptosis. It is possible that such combined therapy could become a new strategy to defeat T1DM in humans.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2006.03.177