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02-09-2010 | Diabetes | Article

Elevated blood glucose disrupts normal immune responses in diabetics

Abstract

Free abstract

MedWire News: UK researchers suggest that elevated blood glucose levels in patients with diabetes can cause competitive inhibition of immune receptors and hinder the body's ability to fight infection.

"These findings provide novel mechanistic explanations for many pathological complications associated with diabetes, especially when glucose levels are difficult to control," comment Daniel Mitchell, from Warwick University, and colleagues.

They researchers explain that immune system receptors, such as C-type lectin, normally bind mannose and fucose molecules found on the cell walls of pathogens.

"Glucose circulates predominantly in its thermodynamically stable pyranoside configuration, and in this cyclic form, it possesses biochemical features common to other carbohydrate molecules in the body such as... bacterial cell wall substructures," they add.

Mitchell et al tested the carbohydrate-binding ability of the immune receptors lectin, DC-SIGN, DC-SIGNR, and surfactant protein (SP)-D in an in vitro environment with glucose concentrations lower than and similar to the blood glucose concentrations of diabetics.

As reported in the journal Immunobiology, the researchers found that high glucose concentrations inhibited the binding of high-mannose glycoprotein to C-type lectin and the binding of DC-SIGN to ligands with fucose molecules.

In addition, complement activation was also inhibited at high glucose concentrations.

The team explains that the binding of C-type lectin to sugar molecules, namely mannose, also assists the process of removing apoptotic cells from the circulation. The presence of high blood glucose therefore prevents this action and may increase the risk for chronic inflammatory diseases.

The researchers conclude: "Further elucidation of C-type lectin function, susceptibility to glucose, and participation within metabolic circuits herald exciting opportunities for discovery within metabolic disease."

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Lauretta Ihonor