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Review
. 2017;18(9):1095-1103.
doi: 10.2174/1389450118666170130145514.

TXNIP in Metabolic Regulation: Physiological Role and Therapeutic Outlook

Naif Mohammad Alhawiti  1 , Saeed Al Mahri  1 , Mohammad Azhar Aziz  2 , Shuja Shafi Malik  1 , Sameer Mohammad  1
Affiliations
Review

TXNIP in Metabolic Regulation: Physiological Role and Therapeutic Outlook

Naif Mohammad Alhawiti et al. Curr Drug Targets. 2017.

Abstract

Background & 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.

Summary: 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.

Keywords: Diabetes mellitus; insulin resistance; metabolic homoeostasis; oxidative stress; pancreatic β-cell dysfunction; thioredoxin system; thioredoxin-interacting protein.

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Figures

Fig. (1)
Fig. (1)
TXNIP reduces the activity of thioredoxin system by direct interaction with thioredoxin (TXN) protein.
Fig. (2)
Fig. (2)
TXNIP controls multiple aspects of energy metabolism by regulating key processes in adipose, brain, liver, muscle and pancreatic β-cells.
Fig. (3)
Fig. (3)
TXNIP controls glucose metabolism by inhibiting both its uptake and breakdown by cells.
Fig. (4)
Fig. (4)
TXNIP regulates the expression of several micro RNAs to control multiple aspects of pancreatic β-cell biology.
See this image and copyright information in PMC

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