Journal
DIABETOLOGIA
Volume 53, Issue 7, Pages 1395-1405Publisher
SPRINGER
DOI: 10.1007/s00125-010-1707-y
Keywords
Chemokine; Cytokine; Endoplasmic reticulum; Fatty acid; Inflammation; Interleukin-1 beta; Islet; Palmitate; Pancreatic beta cell; Type 2 diabetes
Categories
Funding
- European Union
- Belgian Program on Interuniversity Poles of Attraction
- Fonds National de la Recherche Scientifique (FNRS)
- Fonds de la Recherche Scientifique Medicale (FRSM)
- Actions de Recherche Concertes de la Communaute Francaise, Belgium
Ask authors/readers for more resources
Beta cell failure is a crucial component in the pathogenesis of type 2 diabetes. One of the proposed mechanisms of beta cell failure is local inflammation, but the presence of pancreatic islet inflammation in type 2 diabetes and the mechanisms involved remain under debate. Chemokine and cytokine expression was studied by microarray analysis of laser-capture microdissected islets from pancreases obtained from ten non-diabetic and ten type 2 diabetic donors, and by real-time PCR of human islets exposed to oleate or palmitate at 6 or 28 mmol/l glucose. The cellular source of the chemokines was analysed by immunofluorescence of pancreatic sections from individuals without diabetes and with type 2 diabetes. Microarray analysis of laser-capture microdissected beta cells showed increased chemokine and cytokine expression in type 2 diabetes compared with non-diabetic controls. The inflammatory response in type 2 diabetes was mimicked by exposure of non-diabetic human islets to palmitate, but not to oleate or high glucose, leading to the induction of IL-1 beta, TNF-alpha, IL-6, IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1) and chemokine (C-C motif) ligand 2 (CCL2). Interference with IL-1 beta signalling abolished palmitate-induced cytokine and chemokine expression but failed to prevent lipotoxic human islet cell death. Palmitate activated nuclear factor kappa B (NF-kappa B) in human pancreatic beta and non-beta cells, and chemically induced endoplasmic reticulum stress caused cytokine expression and NF-kappa B activation similar to that occurring with palmitate. Saturated-fatty-acid-induced NF-kappa B activation and endoplasmic reticulum stress may contribute to IL-1 beta production and mild islet inflammation in type 2 diabetes. This inflammatory process does not contribute to lipotoxicity ex vivo, but may lead to local chemokine release.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available