Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo.
Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo.
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脂质加速胰岛淀粉样多肽原纤维化加重体内外胰岛损伤
DOI：
10.1186/s12944-018-0694-8
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发表时间：
2018-03-09
影响因子：
4.5
通讯作者：
Jing YH
中科院分区：
文献类型：
--
作者：
Mo XD;Gao LP;Wang QJ;Yin J;Jing YH
研究背景胰岛淀粉样多肽(IAPP)的纤维化引发淀粉样蛋白沉积，进而加剧胰岛质量的损失。然而，尚不清楚什么因素是原纤维形成发展的决定因素。本研究的目的是探讨脂质对IAPP原纤维的影响及其对胰岛的损伤。方法采用硫代黄素-T荧光测定法和透射电镜技术检测人IAPP原纤维形式（hIAPP）与棕榈酸酯在25℃下孵育5小时后的原纤维形式。通过分析细胞膜渗漏和细胞凋亡来评估原纤维 hIAPP 在 INS-1 细胞中的细胞毒性。采用小剂量链脲佐菌素联合高脂饲料喂养两个月诱导大鼠2型糖尿病(T2DM)动物模型。处死前测量血浆生化参数。分离胰岛以评估其功能。结果结果显示hIAPP和棕榈酸酯共孵育诱导更多的原纤维形成。在 INS-1 细胞系中，原纤维 hIAPP 诱导细胞损伤，包括细胞膜渗漏和细胞凋亡，并伴有胰岛素 mRNA 减少。在体内，与对照组相比，T2DM 大鼠的血浆葡萄糖、甘油三酯、rIAPP 和胰岛素升高。此外，T2DM 大鼠胰岛中 IAPP 和胰岛素 mRNA 增加。此外，T2DM还诱导胰岛胰岛素受体表达减少和Caspase-3裂解过度表达。结论体内和体外结果表明脂质和IAPP对胰岛细胞损伤具有协同作用，这可能会增强IAPP表达并加速IAPP原纤维形成。
BackgroundThe fibrillation of islet amyloid polypeptide (IAPP) triggered the amyloid deposition, then enhanced the loss of the pancreatic islet mass. However, it is not clear what factor is the determinant in development of the fibril formation. The aim of this study is to investigate the effects of lipid on IAPP fibril and its injury on pancreatic islet.MethodsThe fibril form of human IAPP (hIAPP) was tested using thioflavin-T fluorescence assay and transmission electron microscope technology after incubated with palmitate for 5 h at 25 °C. The cytotoxicity of fibril hIAPP was evaluated in INS-1 cells through analyzing the leakage of cell membrane and cell apoptosis. Type 2 diabetes mellitus (T2DM) animal model was induced with low dose streptozotocin combined the high-fat diet feeding for two months in rats. Plasma biochemistry parameters were measured before sacrificed. Pancreatic islet was isolated to evaluate their function.ResultsThe results showed that co-incubation of hIAPP and palmitate induced more fibril form. Fibril hIAPP induced cell lesions including cell membrane leakage and cell apoptosis accompanied insulin mRNA decrease in INS-1 cell lines. In vivo, Plasma glucose, triglyceride, rIAPP and insulin increased in T2DM rats compared with the control group. In addition, IAPP and insulin mRNA increased in pancreatic islet of T2DM rats. Furthermore, T2DM induced the reduction of insulin receptor expression and cleaved caspase-3 overexpression in pancreatic islet.ConclusionsResults in vivo and in vitro suggested that lipid and IAPP plays a synergistic effect on pancreatic islet cell damage, which implicated in enhancing the IAPP expression and accelerating the fibril formation of IAPP.
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