Background and aims: CAPN10 gene is associated with type 2 diabetes (T2D). Specific members of the calpain system (CAPN1, CAPN2 and CAPN10) are implicated in glucose metabolism. The aim of this study was to evaluate the calpain activity in leukocytes of control subjects and patients with T2D and its association with the calpain family members involved in glucose metabolism and with biochemical parameters that are altered in T2D.
Methods: Calpain activity under extracellular glucose concentrations (70-280 mg/dL) was evaluated in leukocytes from subjects with and without T2D. Protein and mRNA levels of CAPN1, CAPN2 and CAPN10 were evaluated. Calpain inhibitors assays were performed in leukocytes from subjects without T2D to evaluate glucose uptake. Calpain activity at 100 mg/dL glucose was correlated with biochemical parameters by multivariate regression.
Results: Calpain activity in control subjects increased with extracellular glucose concentration in a dose-dependent manner, showing a negative association with HbA1c levels and total amount of CAPN10 protein. In contrast, calpain activity is decreased in patients with T2D and do not respond to changes in glucose concentration. A reduction of CAPN1 autolytic fragments were observed in the subjects with diabetes. Calpain inhibitors decreased calpain activity but did not altered glucose uptake in leukocytes.
Conclusions: Calpain activity induced by glucose in leukocytes was associated with biochemical markers of glucose metabolism and with CAPN10 protein abundance. Calpain activity is low in subjects with T2D. Thus, calpain activity induced by extracellular glucose in leukocytes could be a potential marker for T2D early risk detection.
Keywords: Calpain activity; Calpain-10; Glucose homeostasis; Leukocytes; Type 2 diabetes.
Copyright © 2019. Published by Elsevier Inc.