Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes

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• 作者：Zandong Yang ; Meng Chen ; Jeffrey D. Carter ; Craig S. Nunemaker ; James C. Garmey ; Sarah D. Kimble and Jerry L. Nadler
• 关键词：Type 1 diabetes ; Lisofylline ; Exendin-4 ; Autoimmunity ; Inflammation ; Cytokine ; β ; -Cell neogenesis ; Proliferation ; Islet ; Non-obese diabetic (NOD) mice
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2006
• 出版时间：9 June 2006
• 年：2006
• 卷：344
• 期：3
• 页码：1017-1022
• 全文大小：2027 K

文摘

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.