Advanced Glycation End-products and Cathepsin Cysteine Protease in Type 2 Diabetic Patients

Introduction: 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.

Objectives: 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.

Patients And Methods: 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.

Results: 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.

Conclusions: 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.