Long-term treatment with EXf, a peptide analog of Exendin-4, improves ¦Â-cell function and survival in diabetic KKAy mice

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• 作者：Guo-jiang Hou ; Cai-na Li ; Shuai-nan Liu ; Yi Huan ; Quan Liu ; Su-juan Sun ; Lin-yi Li ; Shao-cong Hou ; Zhu-fang Shen ; ^{shenzhf@imm.ac.cn} ; ^{shenbamboo@126.com} ; ^{houguojiang1982@126.com}
• 关键词：EXf ; ¦Â-Cell function ; ¦Â-Cell survival ; Proliferation ; Apoptosis ; Diabetic KKAy mice
• 刊名：Peptides
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：40
• 期：Complete
• 页码：123-132
• 全文大小：1961 K

文摘

EXf is a C-terminally truncated fragment of Exendin-4 with two amino acid substitutions. Previous studies showed that EXf controls plasma glucose level acting as a glucagon-like peptide 1 (GLP-1) receptor agonist. The purpose of this study was to evaluate the effects of EXf on ¦Â-cell function and survival in diabetic KKAy mice. EXf treatment significantly improved the glucose intolerance and reduced non-fasting and fasting plasma glucose levels, as well as plasma triglyceride levels in diabetic KKAy mice. In hyperglycemic clamp test, EXf-treated mice displayed an increased glucose infusion rate and first-phase insulin secretion. Treatment with EXf also led to a significant restoration of islet morphology, an increase in Ki67 expression in ¦Â-cells, and a reduction in the number of TUNEL positive ¦Â-cells. In the pancreas, comparative transcription analysis showed up-regulation of Akt1. The up-regulation of phosphorylated Akt1 was confirmed by Western blot, and changes in the protein levels of members of the Akt1 pathway, such as PI3K, Bim, Bcl-2, Bax, Caspase-3, and Caspase-9, PDX-1, were observed as well. Therefore, EXf treatment could improve ¦Â-cell function and survival in diabetic KKAy mice, likely as a result of islet morphology restoration, stimulation of ¦Â-cell proliferation, and inhibition of ¦Â-cell apoptosis.