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Dissociated insulin and islet amyloid polypeptide secretion from isolated rat pancreatic islets cocultured with human pancreatic adenocarcinoma cells.

机译:从与人胰腺腺癌细胞共培养的分离的大鼠胰岛中分离的胰岛素和胰岛淀粉样多肽分泌。

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摘要

Abnormal insulin and islet amyloid polypeptide (IAPP) secretion are usually seen in patients with exocrine pancreatic cancer. The beta-cell dysfunction is a characteristic of the glucose intolerance found in pancreatic cancer patients. The effects of pancreatic cancer cells on insulin and IAPP secretion from beta cells are unclear. In this study, isolated rat pancreatic islets were cocultured with two human pancreatic adenocarcinoma cell lines (Panc-1 and HPAF) and a human colonic adenocarcinoma cell line (HT-29). As a control, islets were incubated in the absence of malignant cells. The accumulation of insulin and IAPP in culture media was measured by radioimmunoassay. Output of insulin and IAPP was decreased in islets cocultured with each malignant cell line. Molar ratio of secreted IAPP and insulin (IAPP/insulin) was increased in the islets cocultured with Panc-1 or HPAF cells, but not HT-29 cells. The decreased insulin and IAPP secretion were partly recovered after Panc-1, HPAF, or HT-29 cells were removed. The IAPP/insulin ratio was normalized after the removal of Panc-1 or HPAF cells. This study indicates that insulin and IAPP secretion are altered by the human adenocarcinoma cells investigated. The impairment induced by pancreatic adenocarcinoma cells is associated with a hypersecretion of IAPP relative to insulin on a molar basis.
机译:外分泌型胰腺癌患者通常会出现胰岛素和胰岛淀粉样多肽(IAPP)分泌异常。 β细胞功能异常是胰腺癌患者中发现的葡萄糖不耐症的特征。胰腺癌细胞对β细胞胰岛素和IAPP分泌​​的影响尚不清楚。在这项研究中,分离的大鼠胰岛与两种人类胰腺腺癌细胞系(Panc-1和HPAF)和人类结肠腺癌细胞系(HT-29)共培养。作为对照,在不存在恶性细胞的情况下孵育胰岛。通过放射免疫测定法测量培养基中胰岛素和IAPP的积累。在与每种恶性细胞系共培养的胰岛中,胰岛素和IAPP的输出减少。与Panc-1或HPAF细胞(而非HT-29细胞)共培养的胰岛中,分泌的IAPP和胰岛素的摩尔比(IAPP /胰岛素)增加。除去Panc-1,HPAF或HT-29细胞后,胰岛素和IAPP分泌​​的减少部分恢复。去除Panc-1或HPAF细胞后,将IAPP /胰岛素比率标准化。这项研究表明,所研究的人类腺癌细胞会改变胰岛素和IAPP的分泌。胰腺腺癌细胞诱导的损伤与IAPP相对于胰岛素的摩尔分泌过多有关。

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