Minireview: Thioredoxin-Interacting Protein: Regulation and Function in the Pancreatic β-Cell

Pancreatic beta-cells are responsible for insulin production, and loss of functional beta-cell mass is now recognized as a critical step in the pathogenesis of both type 1 and type 2 diabetes. However, the factors controlling the life and death of the pancreatic beta-cell have only started to be elucidated. Discovered as the top glucose-induced gene in a human islet microarray study 12 years ago, thioredoxin-interacting protein (TXNIP) has now emerged as such a key player in pancreatic beta-cell biology. Since then, beta-cell expression of TXNIP has been found to be tightly regulated by multiple factors and to be dramatically increased in diabetic islets. Elevated TXNIP levels induce beta-cell apoptosis, whereas TXNIP deficiency protects against type 1 and type 2 diabetes by promoting beta-cell survival. TXNIP interacts with and inhibits thioredoxin and thereby controls the cellular redox state, but it also belongs to the beta-arrestin family of proteins and regulates a variety of metabolic processes. Most recently, TXNIP has been discovered to control beta-cell microRNA expression, beta-cell function, and insulin production. In this review, the current state of knowledge regarding regulation and function of TXNIP in the pancreatic beta-cell and the implications for drug development are discussed.