Therapeutic Potential of Alpha-1 Antitrypsin in Type 1 and Type 2 Diabetes Mellitus

Park, Sangmi S.; Ortega, Romy Rodriguez; Agudelo, Christina W.; Perez, Jessica Perez; Gandara, Brais Perez; García-Arcos, Itsaso; McCarthy, Cormac; Geraghty, Patrick

doi:10.3390/medicina57040397

Cited by 12 publications

(6 citation statements)

References 83 publications

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“…demonstrated the potential role of AAT therapy as an anti-inflammatory agent in the prevention of type 1 diabetes, which was consistent with the results of this study. [ 10 ] Kalis et al . [ 15 ] showed that AAT increases insulin secretion and also protects β-cells against apoptosis-inducing cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence have showed that over-expression of AAT by gene delivery reduced insulitis and inhibited the progression of overt hyperglycemia in non-obese diabetic (NOD) mice. [ 9 10 ] Furthermore, studies have indicated prolongs pancreatic islet allograft survival by administration of pharmaceutical dosages of human AAT and shows islet-related cytoprotective impacts. [ 11 ] Although the underlying mechanism of AAT in producing these positive therapeutic outcomes is not fully understood, recent trials have shown that AAT treatment can inhibit caspase-3 activity and, as a result, protects pancreatic β-cell against apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of alpha 1- antitrypsin activity and phenotype in type 1 diabetic patients to healthy individuals

Khoshdel

Ghoreishi

Mahmoodi

2022

Journal of Family Medicine and Primary Care

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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 ( P < 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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison of alpha 1- antitrypsin activity and phenotype in type 1 diabetic patients to healthy individuals

Khoshdel

Ghoreishi

Mahmoodi

2022

Journal of Family Medicine and Primary Care

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“…AAT regulates fatty acid oxidation, energy expenditure and AMP-activated protein kinase processes. AAT-targeted therapies are playing an increasing role in the treatment of T1DM [70]. They may be useful in treating existing T1DM but also in slowing the progression of newly diagnosed T1DM.…”

Section: Potential Impact On T2dm Of Drugs Used To Treat Copdmentioning

confidence: 99%

Hyperglycaemia and Chronic Obstructive Pulmonary Disease

Cazzola,

Rogliani,

Ora

et al. 2023

Diagnostics

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Chronic obstructive pulmonary disease (COPD) may coexist with type 2 diabetes mellitus (T2DM). Patients with COPD have an increased risk of developing T2DM compared with a control but, on the other side, hyperglycaemia and DM have been associated with reduced predicted levels of lung function. The mechanistic relationships between these two diseases are complicated, multifaceted, and little understood, yet they can impact treatment strategy. The potential risks and benefits for patients with T2DM treated with pulmonary drugs and the potential pulmonary risks and benefits for patients with COPD when taking antidiabetic drugs should always be considered. The interaction between the presence and/or treatment of COPD, risk of infection, presence and/or treatment of T2DM and risk of acute exacerbations of COPD (AECOPDs) can be represented as a vicious circle; however, several strategies may help to break this circle. The most effective approach to simultaneously treating T2DM and COPD is to interfere with the shared inflammatory substrate, thus targeting both lung inflammation (COPD) and vascular inflammation (DM). In any case, it is always crucial to establish glycaemic management since the reduction in lung function found in people with diabetes might decrease the threshold for clinical manifestations of COPD. In this article, we examine possible connections between COPD and T2DM as well as pharmacological strategies that could focus on these connections.

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“…A growing body of evidence from preclinical studies has demonstrated that AAT may have therapeutic potential in autoimmune diseases. AAT activity is altered in both developing and established type I diabetes mellitus, as well as in established type II diabetes [ 174 ]. Promising results from murine models of pancreatic allograft transplantation [ 175 , 176 ] have culminated in clinical trials for onset type I diabetes (NCT02093221 and NCT01183468) [ 137 , 177 , 178 ].…”

Section: Aat Augmentation Therapymentioning

confidence: 99%

A Review of Alpha-1 Antitrypsin Binding Partners for Immune Regulation and Potential Therapeutic Application

O’Brien

Murray

Gogoi

et al. 2022

IJMS

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Alpha-1 antitrypsin (AAT) is the canonical serine protease inhibitor of neutrophil-derived proteases and can modulate innate immune mechanisms through its anti-inflammatory activities mediated by a broad spectrum of protein, cytokine, and cell surface interactions. AAT contains a reactive methionine residue that is critical for its protease-specific binding capacity, whereby AAT entraps the protease on cleavage of its reactive centre loop, neutralises its activity by key changes in its tertiary structure, and permits removal of the AAT-protease complex from the circulation. Recently, however, the immunomodulatory role of AAT has come increasingly to the fore with several prominent studies focused on lipid or protein-protein interactions that are predominantly mediated through electrostatic, glycan, or hydrophobic potential binding sites. The aim of this review was to investigate the spectrum of AAT molecular interactions, with newer studies supporting a potential therapeutic paradigm for AAT augmentation therapy in disorders in which a chronic immune response is strongly linked.

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Therapeutic Potential of Alpha-1 Antitrypsin in Type 1 and Type 2 Diabetes Mellitus

Cited by 12 publications

References 83 publications

Comparison of alpha 1- antitrypsin activity and phenotype in type 1 diabetic patients to healthy individuals

Comparison of alpha 1- antitrypsin activity and phenotype in type 1 diabetic patients to healthy individuals

Hyperglycaemia and Chronic Obstructive Pulmonary Disease

A Review of Alpha-1 Antitrypsin Binding Partners for Immune Regulation and Potential Therapeutic Application

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