Unraveling the relationship among insulin resistance, IGF-1, and amyloid-beta 1-40: Is the definition of type 3 diabetes applicable in the cardiovascular field?

Life Sci. 2024 Sep 1:352:122911. doi: 10.1016/j.lfs.2024.122911. Epub 2024 Jul 11.

Abstract

The concept of "type 3 diabetes" has emerged to define alterations in glucose metabolism that predispose individuals to the development of Alzheimer's disease (AD). Novel evidence suggests that changes in the insulin/insulin-like growth factor 1 (IGF-1)/growth hormone (GH) axis, which are characteristic of Diabetes Mellitus, are one of the major factors contributing to excessive amyloid-beta (Aβ) production and neurodegenerative processes in AD. Moreover, molecular findings suggest that insulin resistance and dysregulated IGF-1 signaling promote atherosclerosis via endothelial dysfunction and a pro-inflammatory state. As the pathophysiological role of Aβ1-40 in patients with cardiovascular disease has attracted attention due to its involvement in plaque formation and destabilization, it is of great interest to explore whether a paradigm similar to that in AD exists in the cardiovascular field. Therefore, this review aims to elucidate the intricate interplay between insulin resistance, IGF-1, and Aβ1-40 in the cardiovascular system and assess the applicability of the type 3 diabetes concept. Understanding these relationships may offer novel therapeutic targets and diagnostic strategies to mitigate cardiovascular risk in patients with insulin resistance and dysregulated IGF-1 signaling.

Keywords: Amyloid-beta; Atherosclerosis; IGF-1; Insulin; Insulin resistance; Type 3 diabetes.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides* / metabolism
  • Animals
  • Cardiovascular Diseases* / metabolism
  • Humans
  • Insulin Resistance* / physiology
  • Insulin-Like Growth Factor I* / metabolism
  • Peptide Fragments* / metabolism

Substances

  • Insulin-Like Growth Factor I
  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • IGF1 protein, human