The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients
The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients
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DOI：
10.1007/s00125-007-0816-8
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发表时间：
2007-12-01
期刊：
影响因子：
8.2
通讯作者：
Cnop, M.
中科院分区：
文献类型：
--
作者：
Marchetti, P.;Bugliani, M.;Cnop, M.
目的/假设胰腺β细胞具有高度发达的内质网（ER），这是由于它们在胰岛素分泌中的作用。由于内质网应激与β细胞功能障碍有关，我们研究了人类2型糖尿病β细胞内质网的几个特征。方法对非糖尿病对照组（ND）和2型糖尿病患者的胰腺和/或离体胰岛进行胰岛素分泌、细胞凋亡（电镜和ELISA）、形态学ER评估（电镜）以及激光捕获显微解剖制备的β细胞和离体胰岛内质网应激标志物的表达。结果2型糖尿病胰岛胰岛素释放较低，β细胞凋亡较高。2型糖尿病β细胞内质网密度体积显著增加。通过微阵列和/或实时逆转录酶聚合酶链反应（RT-PCR）评估α -甘露糖苷酶（也称为甘露糖苷酶，α， 1A类，成员1）和udp -葡萄糖糖蛋白葡萄糖基转移酶样2 （UGCGL2）的表达在ND和2型糖尿病β细胞之间存在差异。免疫球蛋白重链结合蛋白（BiP，也称为热休克70 kDa蛋白5[葡萄糖调节蛋白，78 kDa] [HSPA5]）、X-box结合蛋白1 （XBP- 1，也称为XBP1）和C/EBP同源蛋白（CHOP，也称为损伤诱导转录物3 [DDIT3]）在5.5 mmol/l葡萄糖培养的2型糖尿病β细胞或离体胰岛（微阵列和实时RT-PCR）中的表达不高于ND样品。在11.1 mmol/l葡萄糖条件下培养胰岛24 h， 2型糖尿病胰岛诱导BiP和XBP- 1表达，ND胰岛不诱导。结论/解释在维持生理葡萄糖浓度的胰腺样本或离体胰岛中研究，2型糖尿病的β细胞显示出适度的内质网应激迹象。然而，暴露于葡萄糖水平升高诱导2型糖尿病胰岛细胞内质网应激标志物，因此可能更容易受到代谢扰动引起的内质网应激的影响。
Aims/hypothesis Pancreatic beta cells have highly developed endoplasmic reticulum (ER) due to their role in insulin secretion. Since ER stress has been associated with beta cell dysfunction, we studied several features of beta cell ER in human type 2 diabetes.Methods Pancreatic samples and/ or isolated islets from non- diabetic controls (ND) and type 2 diabetes patients were evaluated for insulin secretion, apoptosis (electron microscopy and ELISA), morphometric ER assessment (electron microscopy), and expression of ER stress markers in beta cell prepared by laser capture microdissection and in isolated islets.Results Insulin release was lower and beta cell apoptosis higher in type 2 diabetes than ND islets. ER density volume was significantly increased in type 2 diabetes beta cells. Expression of alpha- mannosidase (also known as mannosidase, alpha, class 1A, member 1) and UDP-glucose glycoprotein glucosyl transferase like 2 (UGCGL2), assessed by microarray and/ or real-time reverse transcriptase polymerase chain reaction (RT-PCR), differed between ND and type 2 diabetes beta cells. Expression of immunoglobulin heavy chain binding protein (BiP, also known as heat shock 70 kDa protein 5 [glucose- regulated protein, 78 kDa] [HSPA5]), X-box binding protein 1 (XBP- 1, also known as XBP1) and C/EBP homologous protein (CHOP, also known as damage- inducible transcript 3 [DDIT3]) was not higher in type 2 diabetes beta cell or isolated islets cultured at 5.5 mmol/l glucose (microarray and real- time RT-PCR) than in ND samples. When islets were cultured for 24 h at 11.1 mmol/l glucose, there was induction of BiP and XBP- 1 in type 2 diabetes islets but not in ND islets.Conclusions/interpretation Beta cell in type 2 diabetes showed modest signs of ER stress when studied in pancreatic samples or isolated islets maintained at physiological glucose concentration. However, exposure to increased glucose levels induced ER stress markers in type 2 diabetes islet cells, which therefore may be more susceptible to ER stress induced by metabolic perturbations.