Chitotriosidase activity predicts endothelial dysfunction in type-2 diabetes mellitus

Abstract

The enzyme chitotriosidase (ChT) is secreted by activated macrophages and play active role in human immune response. ChT activity is increased in atherosclerosis in association to the extent of the disease. We investigated the relevance of ChT to endothelial functions and insulin resistance in patients with T2DM. Forty newly diagnosed and untreated patients with T2DM (male 17; age 47.0 ± 6.2 years) and 50 healthy volunteers (male 21; age 50.2 ± 8.8 years) were enrolled. Plasma asymmetric dimethyl arginine (ADMA) levels were determined by ELISA. ChT activity was measured by the fluorescence method. Insulin resistance was calculated by the HOMA-IR formula. The patients had higher systolic blood pressures, HOMA-IR, ADMA levels, and ChT activities (P < 0.001 for all) and lower HDL cholesterol levels (P = 0.03) than the control group. The ChT activities of the total group were significantly correlated to the age (r = 0.031, p = 0.003), ADMA (r = 0.22, p = 0.04), and plasma glucose levels (r = 0.27, p = 0.01). ChT was the independent determinant of the plasma ADMA levels (r = 0.26, p = 0.02). The results of this study show that serum ChT activity is increased in patients with newly diagnosed, untreated, and uncomplicated patients with T2DM. The results also imply that increased ChT activity may be a predictor of endothelial dysfunction.

Chitotriosidase: A New Inflammatory Marker in Diabetic Complications

“…In this light, the relationship we observed of all examined GH18 proteins with LE may indicate their connection with progression of late vascular complications [16]. The results imply that increased CHIT1 activity may be a predictor of endothelial dysfunction [15]. …”

“…Nowadays, there is little evidence showing that serum CHIT1 activity is increased in patients with newly diagnosed, untreated, and uncomplicated type 2 DM (T2DM) [15,16]. A recent study reported involvement of neutrophils in the pathogenesis of insulin resistance.…”

Role of Chitotriosidase (Chitinase 1) Under Normal and Disease Conditions

“…Serum CHIT1 activity is increased in patients with newly diagnosed, untreated, and uncomplicated type 2 DM. This elevation is positively associated with the age, plasma glucose, and asymmetric dimethylarginine (ADMA) levels of those patients [76]. ADMA is naturally occurring component of human blood plasma as an analogue of Larginine, and is formed as a metabolic byproduct of protein turnover in any cell types of the human body [75].…”

“…Elevated levels of ADMA inhibit nitric oxide synthesis and impair endothelial function; these levels are increased in patients with DM [75]. The correlation between elevated CHIT1 and ADMA levels could be a sharp biomarker of predicting endothelial dysfunction, which contributes to progression of atherosclerotic lesions, in type 2 DM patients [76]. …”

Effect of PPAR-γ agonists on macrophage activation in type2 diabetes mellitus

“…Malaguernera et al showed that Chitotriosidase activity and the levels of CHIT mRNA increased by stimulation of macrophages with IFN-γ, TNF-α, and LPS [19]. Although an increase in chitotriosidase activity, as well as inflammatory molecules in patients with DM, has been shown], so far there is no data on the effect of PPAR-γ activation on chitotriosidase activity in patients with insulin resistance [20]. Rosiglitazone treatment increased chitotriosidase activity which is released from activated macrophages probably due to PPAR-γ activation-induced expression of scavenger receptors (CD36) and increased uptake of oxLDL in macrophages [11].…”