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TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients

Loss of pancreatic β–cell is a critical factor in the pathogenesis of type 1 diabetes and it also occurs in type 2. TXNIP (thioredoxin – interacting protein), also known as vitamin D3-upregulated protein 1, or thioredoxin-binding-protein-2, regulates this process and modulates cellular redox balance...

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Autores principales: Borowiec, Agnieszka Magdalena, Właszczuk, Adam, Olakowska, Edyta, Lewin-Kowalik, Joanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Iuliu Hatieganu University of Medicine and Pharmacy 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387585/
https://www.ncbi.nlm.nih.gov/pubmed/36060506
http://dx.doi.org/10.15386/mpr-2187
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author Borowiec, Agnieszka Magdalena
Właszczuk, Adam
Olakowska, Edyta
Lewin-Kowalik, Joanna
author_facet Borowiec, Agnieszka Magdalena
Właszczuk, Adam
Olakowska, Edyta
Lewin-Kowalik, Joanna
author_sort Borowiec, Agnieszka Magdalena
collection PubMed
description Loss of pancreatic β–cell is a critical factor in the pathogenesis of type 1 diabetes and it also occurs in type 2. TXNIP (thioredoxin – interacting protein), also known as vitamin D3-upregulated protein 1, or thioredoxin-binding-protein-2, regulates this process and modulates cellular redox balance. TXNIP is localized primarily in the nucleus, but under oxidative stress it moves to mitochondria, where it interacts with mitochondrial thioredoxin 2. Overexpression of TXNIP induced by hyperglycaemia is typical for diabetes and insulin resistance and leads to apoptosis of pancreatic β–cell, cardiomyopathy, metabolic disorders and multiple harmful effects. It activates NLRP3 inflamasomme and IL–1β, a cytokine involved in type 2 diabetes and insulin resistance. TXNIP influences peroxisome proliferator-activated receptor alpha transcriptional activity, expression of glucose transporter–1, nitric oxide production in endothelium and insulin production in β–cells. TXNIP overexpression leads to diabetic retinopathy, nephropathy, atherosclerosis, it occurs in cancers and autoimmune diseases, while its deficiency protects β cells. Reduction of TXNIP is an important target in diabetes treatment. In this mechanism insulin, metformin and inhibitors of dipeptydylopeptydase IV are involved. It has been observed that calcium channel blockers (CCB) used in hypertension also inhibit TXNIP expression in cardiomyocytes. L–type channels identification in pancreatic β-cells revealed that CCB inhibit TXNIP expression also in β–cells. For the first time, verapamil was distinguished as an agent that not only inhibits TXNIP expression in pancreatic β-cells, but also enhances β cell survival and function, and possibly prevents diabetes.
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spelling pubmed-93875852022-09-02 TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients Borowiec, Agnieszka Magdalena Właszczuk, Adam Olakowska, Edyta Lewin-Kowalik, Joanna Med Pharm Rep Review Loss of pancreatic β–cell is a critical factor in the pathogenesis of type 1 diabetes and it also occurs in type 2. TXNIP (thioredoxin – interacting protein), also known as vitamin D3-upregulated protein 1, or thioredoxin-binding-protein-2, regulates this process and modulates cellular redox balance. TXNIP is localized primarily in the nucleus, but under oxidative stress it moves to mitochondria, where it interacts with mitochondrial thioredoxin 2. Overexpression of TXNIP induced by hyperglycaemia is typical for diabetes and insulin resistance and leads to apoptosis of pancreatic β–cell, cardiomyopathy, metabolic disorders and multiple harmful effects. It activates NLRP3 inflamasomme and IL–1β, a cytokine involved in type 2 diabetes and insulin resistance. TXNIP influences peroxisome proliferator-activated receptor alpha transcriptional activity, expression of glucose transporter–1, nitric oxide production in endothelium and insulin production in β–cells. TXNIP overexpression leads to diabetic retinopathy, nephropathy, atherosclerosis, it occurs in cancers and autoimmune diseases, while its deficiency protects β cells. Reduction of TXNIP is an important target in diabetes treatment. In this mechanism insulin, metformin and inhibitors of dipeptydylopeptydase IV are involved. It has been observed that calcium channel blockers (CCB) used in hypertension also inhibit TXNIP expression in cardiomyocytes. L–type channels identification in pancreatic β-cells revealed that CCB inhibit TXNIP expression also in β–cells. For the first time, verapamil was distinguished as an agent that not only inhibits TXNIP expression in pancreatic β-cells, but also enhances β cell survival and function, and possibly prevents diabetes. Iuliu Hatieganu University of Medicine and Pharmacy 2022-07 2022-07-26 /pmc/articles/PMC9387585/ /pubmed/36060506 http://dx.doi.org/10.15386/mpr-2187 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
spellingShingle Review
Borowiec, Agnieszka Magdalena
Właszczuk, Adam
Olakowska, Edyta
Lewin-Kowalik, Joanna
TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients
title TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients
title_full TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients
title_fullStr TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients
title_full_unstemmed TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients
title_short TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients
title_sort txnip inhibition in the treatment of diabetes. verapamil as a novel therapeutic modality in diabetic patients
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387585/
https://www.ncbi.nlm.nih.gov/pubmed/36060506
http://dx.doi.org/10.15386/mpr-2187
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