The role of GRB2 in diabetes, diabetes complications and related disorders

Diabetes Obes Metab. 2025 Jan;27(1):23-34. doi: 10.1111/dom.16015. Epub 2024 Oct 30.

Abstract

Growth factor receptor-bound protein 2 (GRB2) is a key adaptor protein involved in multiple signalling pathways, and its dysregulation is associated with various diseases. Type 2 diabetes is a systemic condition characterized by insulin resistance and impaired β-cell function. The complications of diabetes significantly reduce life expectancy and quality of life, imposing a substantial burden on society. However, the role of GRB2 in diabetes and associated complications is largely unknown. Emerging evidence suggests that GRB2 plays a crucial role in insulin resistance, inflammation, immune activation and the regulation of cellular processes such as cell proliferation, growth, metabolism, angiogenesis, apoptosis and differentiation. Dysregulation of GRB2-mediated pathways contributes to the progression of diabetic neuropathy, cognitive dysfunction, nephropathy, retinopathy and related disorders. This review provides a comprehensive overview of the current understanding of the role of GRB2 in diabetes, diabetes complications and related disorders, alongside recent advances in the development of GRB2-targeted therapies. Elucidating the complex role of GRB2 in these disorders provides valuable insights into potential therapeutic strategies targeting GRB2-mediated pathways.

Keywords: GRB2; atherosclerosis; autoimmune diseases; diabetes; diabetes complications; signal transduction.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Complications* / metabolism
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / metabolism
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism
  • Diabetic Neuropathies / etiology
  • Diabetic Neuropathies / metabolism
  • Diabetic Retinopathy / etiology
  • Diabetic Retinopathy / metabolism
  • GRB2 Adaptor Protein* / metabolism
  • Humans
  • Insulin Resistance
  • Signal Transduction*

Substances

  • GRB2 Adaptor Protein
  • GRB2 protein, human