title: Minireview: Thioredoxin-interacting protein: regulation and function in the pancreatic β-cell.
abstract: Pancreatic β-cells are responsible for insulin production, and loss of functional β-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 β-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 β-cell biology. Since then, β-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 β-cell apoptosis, whereas TXNIP deficiency protects against type 1 and type 2 diabetes by promoting β-cell survival. TXNIP interacts with and inhibits thioredoxin and thereby controls the cellular redox state, but it also belongs to the α-arrestin family of proteins and regulates a variety of metabolic processes. Most recently, TXNIP has been discovered to control β-cell microRNA expression, β-cell function, and insulin production. In this review, the current state of knowledge regarding regulation and function of TXNIP in the pancreatic β-cell and the implications for drug development are discussed.
authors.affiliation: Comprehensive Diabetes Center and Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Anath
authors.initials: A
authors.lastname: Shalev
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000502:physiology*; D002470:Cell Survival; D003920:Diabetes Mellitus / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D007004:Hypoglycemic Agents; C486715:TXNIP protein, human