Analysis of global gene expression profiles suggests a role of acute inflammation in type 3C diabetes mellitus caused by pancreatic ductal adenocarcinoma

作者：Gao, Wenchao; Zhou, Yu; Li, Qingyan; Zhou, Quanbo; Tan, Langping; Song, Yadong; Zhao, Xiaohui; Yu, Min; Zheng, Shangyou; Ye, Huilin; Zeng, Bing; Lin, Qing; Zhou, Jiajia; Liu, Yimin; Huang, Huaiqiu; Zhang, Hui; Hu, Xuchu; Li, Zhihua; Dai, Xianhua; Chen, Rufu^*

来源：Diabetologia, 2015, 58(4): 835-844.

DOI：10.1007/s00125-014-3481-8

• Microarray
• Pancreatic cancer
• Pancreatic-cancer-associated diabetes mellitus
• TNFSF13

Pancreatic ductal adenocarcinoma (PDAC) can cause type 3C diabetes, known as PDAC-associated diabetes mellitus (PDAC-DM), but the mechanism is unknown. This study aimed to reveal the mechanism. @@@ PDAC lesions from patients with or without PDAC-DM (n = 4 in each group) were individually profiled for 23,512 mRNAs with microarrays. Bioinformatic analysis and in vivo and in vitro assays were then conducted. @@@ We determined that 2,778 genes were differentially expressed; over-representation of ten genes was validated with quantitative RT-PCR. The analysis of gene ontology showed that the differentially expressed secretory genes were related mainly to inflammation. High levels of a marker of inflammation (C-reactive protein [CRP]) and an inflammatory mediator (TNF super-family member 13 [TNFSF13]) were found in the serum of patients with PDAC-DM. After surgical resection of PDAC lesions, CRP and TNFSF13 levels significantly decreased (p < 0.01). Furthermore, we found that the levels of TNFSF13 in PDAC lesions and TNFSF13 and CRP in serum were significantly correlated with the diabetic status of patients with PDAC-DM (p < 0.01). Assays in vivo showed that after exposure to an inhibitor of inflammation (celecoxib), the fasting blood glucose level in the mouse model of PDAC-DM dramatically decreased from 6.9 +/- 0.1 to 5.6 +/- 0.1 mmol/l in 2-4 days (p < 0.01). @@@ We found that acute inflammation was involved in the pathogenesis of PDAC-DM. We contend that acute inflammation is a potential target for the diagnosis and treatment of PDAC-DM.

• 出版日期2015-4
• 单位中山大学