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Analysis of global gene expression profiles suggests a role of acute inflammation in type 3C diabetes mellitus caused by pancreatic ductal adenocarcinoma.
- Source :
-
Diabetologia [Diabetologia] 2015 Apr; Vol. 58 (4), pp. 835-44. Date of Electronic Publication: 2015 Jan 31. - Publication Year :
- 2015
-
Abstract
- Aims/hypothesis: 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.<br />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.<br />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).<br />Conclusions/interpretation: 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.
- Subjects :
- Aged
Animals
Anti-Inflammatory Agents pharmacology
Blood Glucose metabolism
Carcinoma, Pancreatic Ductal complications
Carcinoma, Pancreatic Ductal diagnosis
Carcinoma, Pancreatic Ductal drug therapy
Case-Control Studies
Cells, Cultured
Computational Biology
Diabetes Mellitus blood
Diabetes Mellitus diagnosis
Diabetes Mellitus prevention & control
Disease Models, Animal
Female
Genetic Association Studies
Humans
Inflammation Mediators blood
Male
Mice, Inbred BALB C
Middle Aged
Pancreatic Neoplasms complications
Pancreatic Neoplasms diagnosis
Pancreatic Neoplasms drug therapy
Pancreatitis, Chronic blood
Pancreatitis, Chronic diagnosis
Pancreatitis, Chronic prevention & control
Polymerase Chain Reaction
Reproducibility of Results
Carcinoma, Pancreatic Ductal genetics
Diabetes Mellitus genetics
Gene Expression Profiling methods
Genetic Markers
Oligonucleotide Array Sequence Analysis
Pancreatic Neoplasms genetics
Pancreatitis, Chronic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0428
- Volume :
- 58
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Diabetologia
- Publication Type :
- Academic Journal
- Accession number :
- 25636208
- Full Text :
- https://doi.org/10.1007/s00125-014-3481-8