Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/93022
標題: Exendin-4, a glucagon-like peptide-1 analogue, improves Listeria monocytogenes infection in diabetic db/db mice
Exendin-4,一種昇糖素類似胜肽-1,改善db/db糖尿病小鼠之李斯特菌感染
作者: Hsien-Yueh Liu
劉獻岳
關鍵字: 糖尿病;Exendin-4;李斯特菌;巨噬細胞;老鼠;diabetes mellitus;Exendin-4;Listeria monocytogenes;macrophage;mice
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Glucose-lowering and insulin-sensitizing actions of exendin-4: studies in obese diabetic (ob/ob, db/db) mice, diabetic fatty Zucker rats, and diabetic rhesus monkeys (Macaca mulatta). Diabetes 48, 1026-1034.
摘要: 
糖尿病在人與動物都會產生相似的症狀,伴侶動物發生糖尿病的機率逐漸上升。糖尿病被認為是感染的風險因子且會因為感染而造成死亡。在本研究裡,以糖尿病治療藥物Exendin-4(一種昇糖素類似胜肽-1)處理db/db糖尿病小鼠在李斯特菌感染的影響。在老年的db/db糖尿病小鼠,觀察到有CD11b+巨噬細胞的數量減少及巨噬細胞內有高脂肪含量且吞噬能力降低的現象。Exendin-4可以降低db/db糖尿病小鼠的巨噬細胞內脂肪含量與增強其吞噬作用進而改善db/db小鼠對抗李斯特菌感染。Exendin-4也改善db/db糖尿病小鼠肥胖及高血糖症狀,且在擬體內試驗(ex vivo)中增加巨噬細胞對細菌清除率。在Exendin-4處理的db/db小鼠受到李斯特菌感染後的肝臟呈現較少的膿瘍。在Exendin-4處理過的db/db糖尿病小鼠分離的巨噬細胞上,我們證實了ABCA1(ATP binding cassette transporter 1)一種膽固醇的傳送器,表現量較高。總之,我們的結果指出Exendin-4藉由調控巨噬細胞內的脂肪含量及吞噬作用來減少糖尿病動物感染的風險。

This diabetes mellitus has similar characteristics in both humans and animals. The incidence of this disease is increasing among companion animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In this study, homozygous diabetic (db/db) mice were infected with Listeria monocytogenes and then treated with the diabetic treatment drug Exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b+ macrophage populations with higher lipid content and lower phagocytic activity were observed. Exendin-4 lowered high lipid levels and enhanced phagocytosis in macrophages from db/db mice infected with L. monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved ex vivo bacteria clearance by macrophages in the diabetic animals. Liver histology examined during L. monocytogenes infection indicated that abscess formation was much milder in Exendin-4 treated db/db mice than in the control animals. Moreover, the expression of ATP binding cassette transporter 1, a sterol transporter, in the macrophages isolated from the Exendin-4 treated db/db mice was higher than the untreated group. Overall, our results indicated that Exendin-4 reduces the risk of infection in diabetic animals by modulating the interaction between intracellular lipids and phagocytic ability of macrophages
URI: http://hdl.handle.net/11455/93022
其他識別: U0005-2807201517040800
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