Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in β cells and mice.
Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in β cells and mice.
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DOI：
10.1053/j.gastro.2012.08.044
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发表时间：
2012-12
期刊：
影响因子：
29.4
通讯作者：
Chari ST
中科院分区：
文献类型：
--
作者：
Aggarwal G;Ramachandran V;Javeed N;Arumugam T;Dutta S;Klee GG;Klee EW;Smyrk TC;Bamlet W;Han JJ;Rumie Vittar NB;de Andrade M;Mukhopadhyay D;Petersen GM;Fernandez-Zapico ME;Logsdon CD;Chari ST
胰腺癌患者新发糖尿病可能是肿瘤分泌产物引起的副肿瘤现象。我们的目的是鉴定胰腺癌的致糖尿病分泌产物。使用微阵列分析，我们鉴定出肾上腺髓质素是胰腺癌患者糖尿病的潜在介质。肾上腺髓质素在胰腺癌细胞系中上调，其中上清液减少β细胞系中的胰岛素信号传导。我们对人胰腺癌和健康胰腺组织（对照）进行定量逆转录聚合酶链反应和免疫组化，以确定肾上腺髓质素信使RNA和蛋白质的表达，分别。我们研究了肾上腺髓质素对β细胞系和小鼠胰岛分泌胰岛素的影响，以及对小鼠胰腺异种移植物葡萄糖耐量的影响。我们测量了胰腺癌患者、2型糖尿病患者和空腹血糖水平正常的个体（对照组）的肾上腺髓质素血浆水平。与对照组相比，胰腺癌样本中肾上腺髓质素信使RNA和蛋白质水平升高。肾上腺髓质素和胰腺细胞系的条件培养基抑制从小鼠分离的β细胞系和胰岛的葡萄糖刺激的胰岛素分泌;小发夹RNA介导的肾上腺髓质素敲低降低了胰腺癌细胞的条件培养基的作用。相反，胰腺癌小鼠肾上腺髓质素的过度表达导致葡萄糖耐受不良。胰腺癌患者的肾上腺髓质素平均血浆水平（毫微微摩尔/升）高于糖尿病患者或对照组。与未患糖尿病的胰腺癌患者相比，患糖尿病的胰腺癌患者的肾上腺髓质素水平更高。肾上腺髓质素在胰腺癌患者中上调，并导致β细胞和小鼠的胰岛素抵抗。
New-onset diabetes in patients with pancreatic cancer is likely to be a paraneoplastic phenomenon caused by tumor-secreted products. We aimed to identify the diabetogenic secretory product(s) of pancreatic cancer Using microarray analysis, we identified adrenomedullin as a potential mediator of diabetes in patients with pancreatic cancer. Adrenomedullin was up-regulated in pancreatic cancer cell lines, in which supernatants reduced insulin signaling in beta cell lines. We performed quantitative reverse-transcriptase polymerase chain reaction and immunohistochemistry on human pancreatic cancer and healthy pancreatic tissues (controls) to determine expression of adrenomedullin messenger RNA and protein, respectively. We studied the effects of adrenomedullin on insulin secretion by beta cell lines and whole islets from mice and on glucose tolerance in pancreatic xenografts in mice. We measured plasma levels of adrenomedullin in patients with pancreatic cancer, patients with type 2 diabetes mellitus, and individuals with normal fasting glucose levels (controls) Levels of adrenomedullin messenger RNA and protein were increased in human pancreatic cancer samples compared with controls. Adrenomedullin and conditioned media from pancreatic cell lines inhibited glucose-stimulated insulin secretion from beta cell lines and islets isolated from mice; the effects of conditioned media from pancreatic cancer cells were reduced by small hairpin RNA-mediated knockdown of adrenomedullin. Conversely, overexpression of adrenomedullin in mice with pancreatic cancer led to glucose intolerance. Mean plasma levels of adrenomedullin (femtomoles per liter) were higher in patients with pancreatic cancer compared with patients with diabetes or controls. Levels of adrenomedullin were higher in patients with pancreatic cancer who developed diabetes compared those who did not. Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in β cells and mice.
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影响因子：
3
作者：
Martínez, A;Elsasser, TH;Cuttitta, F
通讯作者：
Cuttitta, F
影响因子：
7.2
作者：
Damiano, J;Bordier, L;Bauduceau, B
通讯作者：
Bauduceau, B
影响因子：
4.9
作者：
Nishikimi, T;Horio, T;Kangawa, K
通讯作者：
Kangawa, K
DOI：
10.1007/bf02576207
发表时间：
1993-02-01
期刊：
RESEARCH IN EXPERIMENTAL MEDICINE
影响因子：
--
作者：
AHREN, B;ANDRENSANDBERG, A
通讯作者：
ANDRENSANDBERG, A
影响因子：
6.2
作者：
Ogawa, Y;Tanaka, M;Nakamura, Y
通讯作者：
Nakamura, Y