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RESEARCH PRODUCT

Is Autophagy Altered in the Leukocytes of Type 2 Diabetic Patients?

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It is unknown whether autophagy is altered in the leukocytes of type 2 diabetes (T2D) patients and whether oxidative and endoplasmic reticulum (ER) stresses regulate this mechanism. We studied anthropometric and metabolic parameters and evaluated oxidative stress, chromatin condensation, ER stress, and autophagy parameters in leukocytes of 103 T2D patients versus 109 sex- and age-matched controls. Patients showed increases in glucose, insulin, homeostasis model assessment of insulin resistance, and glycated hemoglobin (HbA1c) compared with controls (p < 0.001). Leukocytes displayed enhanced total and mitochondrial reactive oxygen species (ROS), reduced mitochondrial mass, and increased chromatin condensation (p < 0.05). ER stress was also activated in diabetic patients, who displayed augmented glucose-regulated protein 78 kDa (GRP78), phosphorylated eukaryotic translation initiation factor 2, subunit 1 alpha (P-eIF2a), and activating transcription factor 6 (ATF6) levels (p < 0.05). We also observed an increase in the autophagy markers, microtubule-associated protein light chain 3 (LC3)-II and Beclin 1 (p < 0.05), and significant positive correlations between Beclin 1 and total ROS (r = 0.667), GRP78 (r = 0.925) and P-eIF2a (r = 0.644), and between LC3-II and P-eIF2a (r = 0.636) and ATF6 (r = 0.601). Our results lead to the hypothesis that autophagy is activated in the leukocytes of T2D patients and that both oxidative and ER stress signaling pathways may be implicated in the induction of autophagy.