Thioredoxin-Interacting Protein (TXNIP) in Gestational Diabetes Mellitus

Background: Thioredoxin-interacting protein (TXNIP) is a major inhibitor of the thioredoxin (TRX) antioxidant system and an important player in the development and aggravation of intracellular oxidative stress. Although first recognized as a metabolic regulator, recent studies have identified the multifaceted role of this protein in other molecular pathways involving inflammation, apoptosis, and glucose metabolism. Methods: This review aims to highlight the importance of TXNIP in diabetes-related pathophysiology and explore the existing evidence regarding TXNIP's role in GDM-associated pathogenetic mechanisms, revealing common regulatory pathways. Results: Among other complex diseases, TXNIP has been found upregulated in diabetic pancreatic beta cells, thus contributing to diabetes pathogenesis and its related complications. In addition, depletion of TXNIP has been shown to decrease the negative consequences of excessive stress in various cellular systems and diseases, pointing towards a potential therapeutic target. In line with these findings, TXNIP has been investigated in the pathogenesis of Gestational Diabetes Mellitus (GDM), a common pregnancy complication affecting the mother and the neonate. Overexpression of TXNIP has been found in GDM placentas or trophoblast cell lines mimicking GDM conditions and has been associated with key dysregulated mechanisms of GDM pathophysiology, like oxidative stress, inflammation, apoptosis, impaired autophagy, altered trophoblast behavior, and placental morphology. Interestingly, TXNIP has been found upregulated in GDM maternal serum and downregulated in umbilical cord blood, indicating potential compensatory protective mechanisms to GDM-related oxidative stress. Conclusions: Due to its contribution to the regulation of critical cellular processes such as inflammation, metabolism, and apoptosis, TXNIP finds its place in the pathophysiology of gestational diabetes through a currently limited number of scientific reports.