Advanced glycation end-products and cathepsin cysteine protease in type 2 diabetic patients

In type 2 diabetes, chronic hyperglycemia induces multi-faceted disturbances and contributes to late diabetic complications. Nonenzymatic glycation, leading to formation of advanced glycation end-products (AGEs), is one of the most important consequences of hyperglycemia. Alterations in the function of some proteolytic enzymes are also observed in diabetes.

The aim of the study was to assess the changes in and correlations between the plasma levels of AGEs and the activity of a proteolytic enzyme - cysteine cathepsin B - in plasma and neutrophils derived from patients with type 2 diabetes.

In 102 patients with type 2 diabetes and 55 healthy adults, the plasma levels of total AGEs, low-molecular-weight AGEs (LWM-AGEs), and high‑molecular-weight AGEs (HWM-AGEs) as well as cathepsin B activity in plasma and neutrophils were measured by fluorescence methods. Diabetic complications in patients were also evaluated.

Diabetic patients had significantly higher levels and activities of all the parameters compared with the control group. Moreover, in these patients, HMW-AGEs correlated negatively with plasma cathepsin B and LMW-AGEs with neutrophil cathepsin B. In the quartiles of the increasing levels of HMW-AGEs and LMW-AGEs, a successive decrease of cathepsin B in plasma and neutrophils, respectively, was observed. In patients with different late diabetic complications only the plasma level of LMW-AGEs was significantly different.

Our study showed a significant increase of all forms of AGEs and corresponding changes in the activity of cathepsin B, both in plasma and neutrophils. A significant correlation between AGEs and cathepsin B as well as the ambiguous character of their alterations in patients with late diabetic complications indicate that they exert a complex effect on the course of diabetes.