LIGHT/TNFSF14 is increased in patients with type 2 diabetes mellitus and promotes islet cell dysfunction and endothelial cell inflammation in vitro.
Diabetologia
; 59(10): 2134-44, 2016 10.
Article
in En
| MEDLINE
| ID: mdl-27421726
ABSTRACT
AIMS/HYPOTHESIS:
Activation of inflammatory pathways is involved in the pathogenesis of type 2 diabetes mellitus. On the basis of its role in vascular inflammation and in metabolic disorders, we hypothesised that the TNF superfamily (TNFSF) member 14 (LIGHT/TNFSF14) could be involved in the pathogenesis of type 2 diabetes mellitus.METHODS:
Plasma levels of LIGHT were measured in two cohorts of type 2 diabetes mellitus patients (191 Italian and 40 Norwegian). Human pancreatic islet cells and arterial endothelial cells were used to explore regulation and relevant effects of LIGHT in vitro.RESULTS:
Our major findings were (1) in both diabetic cohorts, plasma levels of LIGHT were significantly raised compared with sex- and age-matched healthy controls (n = 32); (2) enhanced release from activated platelets seems to be an important contributor to the raised LIGHT levels in type 2 diabetes mellitus; (3) in human pancreatic islet cells, inflammatory cytokines increased the release of LIGHT and upregulated mRNA and protein levels of the LIGHT receptors lymphotoxin ß receptor (LTßR) and TNF receptor superfamily member 14 (HVEM/TNFRSF14); (4) in these cells, LIGHT attenuated the insulin release in response to high glucose at least partly via pro-apoptotic effects; and (5) in human arterial endothelial cells, glucose boosted inflammatory response to LIGHT, accompanied by an upregulation of mRNA levels of HVEM (also known as TNFRSF14) and LTßR (also known as LTBR). CONCLUSIONS/INTERPRETATION:
Our findings show that patients with type 2 diabetes mellitus are characterised by increased plasma LIGHT levels. Our in vitro findings suggest that LIGHT may contribute to the progression of type 2 diabetes mellitus by attenuating insulin secretion in pancreatic islet cells and by contributing to vascular inflammation.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Islets of Langerhans
/
Diabetes Mellitus, Type 2
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Tumor Necrosis Factor Ligand Superfamily Member 14
/
Inflammation
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Diabetologia
Year:
2016
Type:
Article
Affiliation country:
Norway