title: TXNIP in Metabolic Regulation: Physiological Role and Therapeutic Outlook.
abstract: Background &amp; Objective: Thioredoxin-interacting protein (TXNIP) also known as thioredoxin binding protein-2 is a ubiquitously expressed protein that interacts and negatively regulates expression and function of Thioredoxin (TXN). Over the last few years, TXNIP has attracted considerable attention due to its wide-ranging functions impacting several aspects of energy metabolism. TXNIP acts as an important regulator of glucose and lipid metabolism through pleiotropic actions including regulation of β-cell function, hepatic glucose production, peripheral glucose uptake, adipogenesis, and substrate utilization. Overexpression of TXNIP in animal models has been shown to induce apoptosis of pancreatic β-cells, reduce insulin sensitivity in peripheral tissues like skeletal muscle and adipose, and decrease energy expenditure. On the contrary, TXNIP deficient animals are protected from diet induced insulin resistance and type 2 diabetes.
  
  
  CONCLUSIONS
  Consequently, targeting TXNIP is thought to offer novel therapeutic opportunity and TXNIP inhibitors have the potential to become a powerful therapeutic tool for the treatment of diabetes mellitus. Here we summarize the current state of our understanding of TXNIP biology, highlight its role in metabolic regulation and raise critical questions that could help future research to exploit TXNIP as a therapeutic target.
authors.affiliation: Experimental Medicine, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (NGHA), Riyadh, Saudi Arabia.
authors.forename: Naif Mohammad
authors.initials: NM
authors.lastname: Alhawiti
authors.affiliation: Experimental Medicine, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (NGHA), Riyadh, Saudi Arabia.
authors.forename: Saeed
authors.initials: S
authors.lastname: Al Mahri
authors.affiliation: Colorectal Cancer Research Program, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (NGHA), Riyadh, Saudi Arabia.
authors.forename: Mohammad Azhar
authors.initials: MA
authors.lastname: Aziz
authors.affiliation: Experimental Medicine, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (NGHA), Riyadh, Saudi Arabia.
authors.forename: Shuja Shafi
authors.initials: SS
authors.lastname: Malik
authors.affiliation: Experimental Medicine, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (NGHA), Riyadh, Saudi Arabia.
authors.forename: Sameer
authors.initials: S
authors.lastname: Mohammad
mesh_terms: D050156:Adipogenesis; D002352:Carrier Proteins / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D002352:Carrier Proteins; C486715:TXNIP protein, human; D005947:Glucose
keywords: Diabetes mellitus; insulin resistance; metabolic homoeostasis; oxidative stress; pancreatic
  β-cell dysfunction; thioredoxin system; thioredoxin-interacting protein