Background And Aims: Alpha 1 antitrypsin (AAT) is an inhibitor of serine protease, which has shown anti-inflammatory reactions in a variety of diseases. It has been thought that that AAT plays a role in prolonging islet allograft survival, preventing the development of type 1 diabetes mellitus (T1DM), and hindering β-cell apoptosis of pancreas. In the current examination, the AAT activity in T1DM and healthy individuals was measured using enzymatic assay.
Methods: The present study was conducted on 42 patients with T1DM who referred to the Diabetes Clinic of Rafsanjan, Kerman, Iran, and 42 healthy control individuals who were matched for age, sex and smoking habits. The serum trypsin inhibitory capacity (TIC) was assessed. Plasma samples were analyzed for phenotype, AAT concentration, blood glucose and lipid levels were measured.
Results: The activity of plasma AAT and the serum TIC level of patients with T1DM (2.35 ± 0.34 μmol/min/ml) was significantly lower than healthy participants (3.36 ± 0.36 μmol/min/ml). The frequency of phenotype MM in healthy individual was 100%; and in T1DM patients, the prevalence of phenotype MM, MS and MZ was 61.9%, 23.8% and 14.3%, respectively ( < 0.001).
Conclusions: It was concluded that that the lack of AAT may be related to the increased risk of T1DM developing.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_905_21 | DOI Listing |
ERJ Open Res
January 2025
Kamada Ltd., Rehovot, Israel.
Background: Alpha-1 antitrypsin (AAT)-deficient individuals have a greater risk for developing COPD than individuals with normal AAT levels.
Methods: This was a double-blind, randomised, parallel group, placebo-controlled trial to examine the safety and tolerability of "Kamada-AAT for Inhalation" (inhaled AAT) in subjects with AAT deficiency, and to explore its effect on AAT and biomarkers in the lung epithelial lining fluid (ELF). 36 patients with severe AAT deficiency were randomised 2:1 to receive 80 mg or 160 mg inhaled AAT or placebo once daily for 12 weeks.
Cell Rep Med
January 2025
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA. Electronic address:
Alpha-1 antitrypsin (AAT) deficiency (AATD) is a monogenic disease caused by misfolding of AAT variants resulting in gain-of-toxic aggregation in the liver and loss of monomer activity in the lung leading to chronic obstructive pulmonary disease (COPD). Using high-throughput screening, we discovered a bioactive natural product, phenethyl isothiocyanate (PEITC), highly enriched in cruciferous vegetables, including watercress and broccoli, which improves the level of monomer secretion and neutrophil elastase (NE) inhibitory activity of AAT-Z through the endoplasmic reticulum (ER) redox sensor protein disulfide isomerase (PDI) A4 (PDIA4). The intracellular polymer burden of AAT-Z can be managed by combination treatment of PEITC and an autophagy activator.
View Article and Find Full Text PDFIJTLD Open
January 2025
Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padua, Padua, Italy.
Nat Commun
January 2025
University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Corticosteroid binding globulin (CBG; SERPINA6) binds >85% of circulating glucocorticoids but its influence on their metabolic actions is unproven. Targeted proteolytic cleavage of CBG by neutrophil elastase (NE; ELANE) significantly reduces CBG binding affinity, potentially increasing 'free' glucocorticoid levels at sites of inflammation. NE is inhibited by alpha-1-antitrypsin (AAT; SERPINA1).
View Article and Find Full Text PDFFEBS J
January 2025
Physics, Department of Molecular and Translational Medicine, University of Brescia, Italy.
Neutrophil elastase (NE) is released by activated neutrophils during an inflammatory response and exerts proteolytic activity on elastin and other extracellular matrix components. This protease is rapidly inhibited by the plasma serine protease inhibitor alpha-1-antitrypsin (AAT), and the importance of this protective activity on lung tissue is highlighted by the development of early onset emphysema in individuals with AAT deficiency. As a serpin, AAT presents a surface-exposed reactive centre loop (RCL) whose sequence mirrors the target protease specificity.
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