Title:TXNIP in Metabolic Regulation: Physiological Role and Therapeutic Outlook
Volume: 18
Issue: 9
Author(s): Naif Mohammad Alhawiti, Saeed Al Mahri, Mohammad Azhar Aziz, Shuja Shafi Malik and Sameer Mohammad*
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
Keywords:
Diabetes mellitus, thioredoxin system, thioredoxin-interacting protein, oxidative stress, insulin resistance, pancreatic
β-cell dysfunction, metabolic homoeostasis.
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.
