title: Analysis of global gene expression profiles suggests a role of acute inflammation in type 3C diabetes mellitus caused by pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Hepatopancreatobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 Yanjiang Road, 510120, Guangzhou, People's Republic of China.
authors: Wenchao
authors: W
authors: Gao
authors: Yu
authors: Y
authors: Zhou
authors: Qingyan
authors: Q
authors: Li
authors: Quanbo
authors: Q
authors: Zhou
authors: Langping
authors: L
authors: Tan
authors: Yadong
authors: Y
authors: Song
authors: Xiaohui
authors: X
authors: Zhao
authors: Min
authors: M
authors: Yu
authors: Shangyou
authors: S
authors: Zheng
authors: Huilin
authors: H
authors: Ye
authors: Bing
authors: B
authors: Zeng
authors: Qing
authors: Q
authors: Lin
authors: Jiajia
authors: J
authors: Zhou
authors: Yimin
authors: Y
authors: Liu
authors: Huaiqiu
authors: H
authors: Huang
authors: Hui
authors: H
authors: Zhang
authors: Xuchu
authors: X
authors: Hu
authors: Zhihua
authors: Z
authors: Li
authors: Xianhua
authors: X
authors: Dai
authors: Rufu
authors: R
authors: Chen
mesh_terms: D000368:Aged; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D002478:Cells, Cultured; D019295:Computational Biology; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D056726:Genetic Association Studies; D005819:Genetic Markers; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D050500:Pancreatitis, Chronic / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D005819:Genetic Markers; D018836:Inflammation Mediators
references: Nat Rev Drug Discov. 2014 Jun;13(6):465-76
references: 24854413
references: J Proteomics. 2013 Jun 12;84:52-60
references: 23571023
references: Diabetes Metab Res Rev. 2012 Jul;28(5):388-94
references: 22389088
references: Eur J Intern Med. 2013 Apr;24(3):203-6
references: 23375619
references: Annu Rev Med. 2002;53:35-57
references: 11818462
references: J Endocrinol. 2013 Jan 02;216(1):T1-T15
references: 23160966
references: Nat Rev Mol Cell Biol. 2008 Mar;9(3):193-205
references: 18200017
references: Clin Chem Lab Med. 2011 Oct;49(10):1715-9
references: 21612541
references: PLoS One. 2012;7(5):e38157
references: 22666471
references: Biochem Biophys Res Commun. 1999 Apr 13;257(2):622-8
references: 10198261
references: Gut. 2004 Aug;53(8):1159-66
references: 15247186
references: Int J Cancer. 2014 Jun 1;134(11):2646-55
references: 24615168
references: Diabetes Obes Metab. 2013 Sep;15 Suppl 3:193-6
references: 24003937
references: Pancreas. 2013 May;42(4):622-32
references: 23271396
references: J Clin Lab Anal. 2010;24(4):256-61
references: 20626020
references: Lancet. 2011 Aug 13;378(9791):607-20
references: 21620466
references: Am J Gastroenterol. 2010 Jul;105(7):1661-9
references: 20571492
references: World J Surg Oncol. 2012 Aug 24;10:171
references: 22920886
references: Gastroenterology. 2005 Aug;129(2):504-11
references: 16083707
references: Lancet Oncol. 2009 Jan;10(1):88-95
references: 19111249
references: Diabetes Care. 2013 Jan;36 Suppl 1:S67-74
references: 23264425
references: Anticancer Res. 1995 Nov-Dec;15(6B):2585-8
references: 8669828
references: Cancer Res. 2000 May 1;60(9):2361-4
references: 10811109
references: Proteins. 2001 May 15;43(3):246-55
references: 11288174