Ferroptosis and iron metabolism in diabetes: Pathogenesis, associated complications, and therapeutic implications

Front Endocrinol (Lausanne). 2024 Aug 30:15:1447148. doi: 10.3389/fendo.2024.1447148. eCollection 2024.

Abstract

Diabetes mellitus is a complex chronic disease, considered as one of the most common metabolic disorders worldwide, posing a major threat to global public health. Ferroptosis emerges as a novel mechanism of programmed cell death, distinct from apoptosis, necrosis, and autophagy, driven by iron-dependent lipid peroxidation accumulation and GPx4 downregulation. A mounting body of evidence highlights the interconnection between iron metabolism, ferroptosis, and diabetes pathogenesis, encompassing complications like diabetic nephropathy, cardiomyopathy, and neuropathy. Moreover, ferroptosis inhibitors hold promise as potential pharmacological targets for mitigating diabetes-related complications. A better understanding of the role of ferroptosis in diabetes may lead to an improvement in global diabetes management. In this review, we delve into the intricate relationship between ferroptosis and diabetes development, exploring associated complications and current pharmacological treatments.

Keywords: complications; diabetes; ferroptosis; iron; treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Complications / metabolism
  • Diabetes Mellitus* / metabolism
  • Ferroptosis* / physiology
  • Humans
  • Iron* / metabolism
  • Lipid Peroxidation

Substances

  • Iron

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2023R1A2C3006220 and 2022K2A9A1A06091879 to DR). Open access funding by University of Geneva.