Transglutaminase 2 in diabetes mellitus: Unraveling its multifaceted role and therapeutic implications for vascular complications

Theranostics. 2024 Mar 25;14(6):2329-2344. doi: 10.7150/thno.95742. eCollection 2024.

Abstract

Diabetes, a severe metabolic disease characterized by chronic hypoglycemia, poses debilitating and life-threatening risks of microvascular and macrovascular complications, including blindness, kidney failure, heart attacks, and limb amputation. Addressing these complications is paramount, urging the development of interventions targeting diabetes-associated vascular dysfunctions. To effectively combat diabetes, a comprehensive understanding of the pathological mechanisms underlying complications and identification of precise therapeutic targets are imperative. Transglutaminase 2 (TGase2) is a multifunctional enzyme implicated in the pathogenesis of diverse diseases such as neurodegenerative disorders, fibrosis, and inflammatory conditions. TGase2 has recently emerged as a key player in both the pathogenesis and therapeutic intervention of diabetic complications. This review highlights TGase2 as a therapeutic target for diabetic complications and explores TGase2 inhibition as a promising therapeutic approach in their treatment.

Keywords: diabetic complications; hyperglycemic memory; inhibitors; transglutaminase 2; vascular leakage.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Complications
  • Diabetes Mellitus
  • Diabetic Angiopathies
  • GTP-Binding Proteins* / metabolism
  • Humans
  • Protein Glutamine gamma Glutamyltransferase 2*
  • Transglutaminases* / antagonists & inhibitors
  • Transglutaminases* / metabolism

Substances

  • Transglutaminases
  • Protein Glutamine gamma Glutamyltransferase 2
  • GTP-Binding Proteins