Diabetes pathogenic mechanisms and potential new therapies based upon a novel target called TXNIP

Curr Opin Endocrinol Diabetes Obes. 2018 Apr;25(2):75-80. doi: 10.1097/MED.0000000000000391.


Purpose of review: Thioredoxin-interacting protein has emerged as a major factor regulating pancreatic β-cell dysfunction and death, key processes in the pathogenesis of type 1 and type 2 diabetes. Accumulating evidence based on basic, preclinical, and retrospective epidemiological research suggests that TXNIP represents a promising therapeutic target for diabetes. The present review is aimed at providing an update regarding these developments.

Recent findings: TXNIP has been shown to be induced by glucose and increased in diabetes and to promote β-cell apoptosis, whereas TXNIP deletion protected against diabetes. More recently, TXNIP inhibition has also been found to promote insulin production and glucagon-like peptide 1 signaling via regulation of a microRNA. β-Cell TXNIP expression itself was found to be regulated by hypoglycemic agents, carbohydrate-response-element-binding protein, and cytosolic calcium or the calcium channel blocker, verapamil. Retrospective studies now further suggest that verapamil use might be associated with a lower incidence of type 2 diabetes in humans.

Summary: TXNIP has emerged as a key factor in the regulation of functional β-cell mass and TXNIP inhibition has shown beneficial effects in a variety of studies. Thus, the inhibition of TXNIP may provide a novel approach to the treatment of diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / physiology*
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / therapy*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Molecular Targeted Therapy* / methods
  • Molecular Targeted Therapy* / trends
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Therapies, Investigational / methods*


  • Carrier Proteins
  • Hypoglycemic Agents
  • Insulin
  • TXNIP protein, human