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Diabetologia. 2009 Aug;52(8):1665-8. doi: 10.1007/s00125-009-1394-8. Epub 2009 May 20.

Increased levels of ligands of Toll-like receptors 2 and 4 in type 1 diabetes.

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  • 1Laboratory for Atherosclerosis and Metabolic Research, UC Davis Medical Center, Sacramento, CA 95817, USA.

Abstract

AIMS/HYPOTHESIS:

Type 1 diabetes is a proinflammatory state characterised by increased levels of circulating biomarkers of inflammation and monocyte activity. We have shown increased Toll-like receptor 2 (TLR2) and TLR4 expression and signalling in monocytes from type 1 diabetic patients. Several endogenous ligands of TLR2 and TLR4 have been identified; however, there is a paucity of data on levels of these endogenous ligands in diabetes. Thus, the aim of this study was to examine circulating levels of exogenous/endogenous ligands of TLR2 and TLR4 in type 1 diabetic patients and to compare these with the levels in matched healthy controls.

METHODS:

Healthy controls (n = 37) and type 1 diabetic patients (n = 34) were recruited, and a fasting blood sample was obtained. Circulating levels of endotoxin, heat-shock protein 60 (Hsp60), high-mobility group box 1 (HMGB1) and growth arrest-specific 6 (GAS6) proteins were assessed by ELISA, and TLR2 and TLR4 expression was determined by flow cytometry.

RESULTS:

Levels of the classical TLR4 ligand, endotoxin, were significantly elevated in type 1 diabetic patients compared with those in matched controls. Hsp60 and HMGB1 concentrations were also significantly increased in the patients (p < 0.01 and p < 0.001, respectively). No significant differences were observed in GAS6.

CONCLUSIONS/INTERPRETATION:

We report the novel observation that levels of ligands of TLR2 and TLR4 are significantly elevated in type 1 diabetes, and this, in concert with hyperglycaemia, accounts for the increase in TLR2 and TLR4 activity, underscoring the proinflammatory state of type 1 diabetes.

PMID:
19455302
[PubMed - indexed for MEDLINE]
PMCID:
PMC2709882
Free PMC Article
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