Thioredoxin-Interacting Protein as a Novel Potential Therapeutic Target in Diabetes Mellitus and Its Underlying Complications

Dawit Zewdu Wondafrash,1 Asmelash Tesfay Nire’a,2 Gebrehiwot Gebremedihn Tafere,1 Desilu Mahari Desta,3 Demoze Asmerom Berhe,4 Kaleab Alemayehu Zewdie1 1Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, Mekelle, Ethiopia; 2Pharmacology and Toxicology Resear...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wondafrash DZ, Nire'a AT, Tafere GG, Desta DM, Berhe DA, Zewdie KA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	diabetes mellitus thioredoxin txnip txnip modulators verapamil Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/e120ff783cf64328b3bfcada75f0a2d6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e120ff783cf64328b3bfcada75f0a2d6
record_format	dspace
spelling	oai:doaj.org-article:e120ff783cf64328b3bfcada75f0a2d62021-12-02T09:10:06ZThioredoxin-Interacting Protein as a Novel Potential Therapeutic Target in Diabetes Mellitus and Its Underlying Complications1178-7007https://doaj.org/article/e120ff783cf64328b3bfcada75f0a2d62020-01-01T00:00:00Zhttps://www.dovepress.com/thioredoxin-interacting-protein-as-a-novel-potential-therapeutic-targe-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Dawit Zewdu Wondafrash,1 Asmelash Tesfay Nire’a,2 Gebrehiwot Gebremedihn Tafere,1 Desilu Mahari Desta,3 Demoze Asmerom Berhe,4 Kaleab Alemayehu Zewdie1 1Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, Mekelle, Ethiopia; 2Pharmacology and Toxicology Research and Course Unit, Department of Pharmacy, Axum University, Axum, Ethiopia; 3Clinical Pharmacy Research and Course Unit, School of Pharmacy, Mekelle University, Mekelle, Ethiopia; 4Department of Medicinal Chemistry, School of Pharmacy, Mekelle University, Mekelle, EthiopiaCorrespondence: Dawit Zewdu WondafrashDepartment of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, P.O. Box: 1871, Mekelle, EthiopiaTel +251910127356Email davaniye@gmail.comAbstract: Diabetes mellitus (DM) is a common metabolic disorder which is characterized by a persistent increment of blood glucose. Globally, DM affects millions of people and the prevalence is increasing alarmingly. The critical step in the pathophysiology of DM is the loss of β-cells of the pancreas, which are responsible for the secretion of insulin. Thioredoxin-interacting protein (TXNIP) is among the factors that control the production and loss of the pancreatic β-cells. TXNIP is an α-arrestin that can bind and inhibit thioredoxin (the antioxidant protein) which is produced in the pancreatic islet after glucose intake. Numerous studies illustrated that elevated TXNIP levels were found to induce β-cell apoptosis; whereas TXNIP deficiency protects against type I and type II diabetes by promoting β-cell survival. Nowadays, TXNIP depletion is becoming a key factor in pancreatic β-cell survival enhancement. In the present review, targeting TXNIP is found to be relevant as a unique therapeutic opportunity, not only to improve insulin secretion and sensitivity, but also ameliorating the long term microvascular and macrovascular complications of the disease. Thus, TXNIP inhibitors that could reduce the expression and/or activity of TXNIP to non-diabetic levels are promising agents to halt the alarming rate of diabetes and its related complications.Keywords: diabetes mellitus, thioredoxin, TXNIP, TXNIP modulators, verapamilWondafrash DZNire'a ATTafere GGDesta DMBerhe DAZewdie KADove Medical Pressarticlediabetes mellitusthioredoxintxniptxnip modulatorsverapamilSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 43-51 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetes mellitus thioredoxin txnip txnip modulators verapamil Specialties of internal medicine RC581-951
spellingShingle	diabetes mellitus thioredoxin txnip txnip modulators verapamil Specialties of internal medicine RC581-951 Wondafrash DZ Nire'a AT Tafere GG Desta DM Berhe DA Zewdie KA Thioredoxin-Interacting Protein as a Novel Potential Therapeutic Target in Diabetes Mellitus and Its Underlying Complications
description	Dawit Zewdu Wondafrash,1 Asmelash Tesfay Nire’a,2 Gebrehiwot Gebremedihn Tafere,1 Desilu Mahari Desta,3 Demoze Asmerom Berhe,4 Kaleab Alemayehu Zewdie1 1Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, Mekelle, Ethiopia; 2Pharmacology and Toxicology Research and Course Unit, Department of Pharmacy, Axum University, Axum, Ethiopia; 3Clinical Pharmacy Research and Course Unit, School of Pharmacy, Mekelle University, Mekelle, Ethiopia; 4Department of Medicinal Chemistry, School of Pharmacy, Mekelle University, Mekelle, EthiopiaCorrespondence: Dawit Zewdu WondafrashDepartment of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, P.O. Box: 1871, Mekelle, EthiopiaTel +251910127356Email davaniye@gmail.comAbstract: Diabetes mellitus (DM) is a common metabolic disorder which is characterized by a persistent increment of blood glucose. Globally, DM affects millions of people and the prevalence is increasing alarmingly. The critical step in the pathophysiology of DM is the loss of β-cells of the pancreas, which are responsible for the secretion of insulin. Thioredoxin-interacting protein (TXNIP) is among the factors that control the production and loss of the pancreatic β-cells. TXNIP is an α-arrestin that can bind and inhibit thioredoxin (the antioxidant protein) which is produced in the pancreatic islet after glucose intake. Numerous studies illustrated that elevated TXNIP levels were found to induce β-cell apoptosis; whereas TXNIP deficiency protects against type I and type II diabetes by promoting β-cell survival. Nowadays, TXNIP depletion is becoming a key factor in pancreatic β-cell survival enhancement. In the present review, targeting TXNIP is found to be relevant as a unique therapeutic opportunity, not only to improve insulin secretion and sensitivity, but also ameliorating the long term microvascular and macrovascular complications of the disease. Thus, TXNIP inhibitors that could reduce the expression and/or activity of TXNIP to non-diabetic levels are promising agents to halt the alarming rate of diabetes and its related complications.Keywords: diabetes mellitus, thioredoxin, TXNIP, TXNIP modulators, verapamil
format	article
author	Wondafrash DZ Nire'a AT Tafere GG Desta DM Berhe DA Zewdie KA
author_facet	Wondafrash DZ Nire'a AT Tafere GG Desta DM Berhe DA Zewdie KA
author_sort	Wondafrash DZ
title	Thioredoxin-Interacting Protein as a Novel Potential Therapeutic Target in Diabetes Mellitus and Its Underlying Complications
title_short	Thioredoxin-Interacting Protein as a Novel Potential Therapeutic Target in Diabetes Mellitus and Its Underlying Complications
title_full	Thioredoxin-Interacting Protein as a Novel Potential Therapeutic Target in Diabetes Mellitus and Its Underlying Complications
title_fullStr	Thioredoxin-Interacting Protein as a Novel Potential Therapeutic Target in Diabetes Mellitus and Its Underlying Complications
title_full_unstemmed	Thioredoxin-Interacting Protein as a Novel Potential Therapeutic Target in Diabetes Mellitus and Its Underlying Complications
title_sort	thioredoxin-interacting protein as a novel potential therapeutic target in diabetes mellitus and its underlying complications
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/e120ff783cf64328b3bfcada75f0a2d6
work_keys_str_mv	AT wondafrashdz thioredoxininteractingproteinasanovelpotentialtherapeutictargetindiabetesmellitusanditsunderlyingcomplications AT nireaat thioredoxininteractingproteinasanovelpotentialtherapeutictargetindiabetesmellitusanditsunderlyingcomplications AT taferegg thioredoxininteractingproteinasanovelpotentialtherapeutictargetindiabetesmellitusanditsunderlyingcomplications AT destadm thioredoxininteractingproteinasanovelpotentialtherapeutictargetindiabetesmellitusanditsunderlyingcomplications AT berheda thioredoxininteractingproteinasanovelpotentialtherapeutictargetindiabetesmellitusanditsunderlyingcomplications AT zewdieka thioredoxininteractingproteinasanovelpotentialtherapeutictargetindiabetesmellitusanditsunderlyingcomplications
_version_	1718398216650620928

Thioredoxin-Interacting Protein as a Novel Potential Therapeutic Target in Diabetes Mellitus and Its Underlying Complications

Ejemplares similares