uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
The synthetic liver X receptor agonist GW3965 reduces tissue factor production and inflammatory responses in human islets in vitro
Show others and affiliations
2009 (English)In: Diabetologia, ISSN 0012-186X, Vol. 52, no 7, 1352-62 p.Article in journal (Refereed) Published
Abstract [en]

AIMS/HYPOTHESIS: Optimising islet culture conditions may be one strategy for reducing islet loss prior to, and immediately after, islet transplantation. Liver X receptor (LXR) agonism has previously been shown to increase insulin release from pancreatic islets and reduce inflammation in leucocytes. Our aim was to investigate whether the synthetic LXR agonist GW3965 could modulate the inflammatory status of human pancreatic islets. METHODS: Levels of pro-inflammatory cytokines and tissue factor in isolated human islets were determined by TaqMan low density array and/or real-time quantitative RT-PCR (mRNA levels) and enzyme immunoassay (EIA) (protein levels). Islet viability was measured using intracellular ATP content, ADP/ATP ratio, mitochondrial dehydrogenase activity (XTT assay) and insulin secretion in a dynamic glucose-challenge model. Apoptosis was determined by EIA measurement of histone-DNA complexes present in cytoplasm and by assaying caspase-3/-7 activity. RESULTS: Treatment of LPS-stimulated human islets with the synthetic LXR agonist GW3965 (1 micromol/l) for 24 h reduced mRNA and protein levels of selected pro-inflammatory cytokines (IL-8, monocyte chemotactic protein-1 and tissue factor). Moreover, GW3965 had no adverse effect on insulin secretion, islet viability or apoptosis. No excess of lipid accumulation could be detected with the dosage and exposure time used. CONCLUSIONS/INTERPRETATION: LXR activation suppresses inflammation in human islets in vitro without adverse effects on islet viability. Short-term moderate activation of LXR prior to islet transplantation may represent a possible strategy for improving post-transplant islet survival.

Place, publisher, year, edition, pages
2009. Vol. 52, no 7, 1352-62 p.
Keyword [en]
Chemokines, Cytokines, GW3965, Human islets, Inflammatory mediators, Liver X receptor, Tissue factor
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-104984DOI: 10.1007/s00125-009-1366-zISI: 000266496000019PubMedID: 19415233OAI: oai:DiVA.org:uu-104984DiVA: diva2:220328
Available from: 2009-05-31 Created: 2009-05-31 Last updated: 2009-06-16Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Department of Oncology, Radiology and Clinical ImmunologyClinical Immunology
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 119 hits
ReferencesLink to record
Permanent link

Direct link