Endothelial IGF-1 Receptor Signalling in Diabetes and Insulin Resistance

Trends Endocrinol Metab. 2016 Feb;27(2):96-104. doi: 10.1016/j.tem.2015.11.009. Epub 2015 Dec 20.

Abstract

Despite contemporary medical therapy, people with diabetes and insulin resistance experience substantially increased risk of cardiovascular events caused by atherosclerosis. Dysfunction of the endothelium is a key phase in early atherogenesis and represents a promising therapeutic target. The evolutionarily related insulin and insulin-like growth factor-1 (IGF-1) axes are implicated in the development of vascular disease. In this review, we summarise recent developments in our understanding of how modulating the IGF-1 axis influences vascular disease in the setting of insulin resistance. By contrasting data from models of altered insulin and/or IGF-1 signalling, we emphasise the complex spatiotemporal interplay of these systems in health and disease. We then discuss therapeutic opportunities, before detailing important gaps in our knowledge relevant to therapeutic translation.

Keywords: diabetes; endothelium; insulin resistance; insulin-like growth factor-1; vascular.

Publication types

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

MeSH terms

  • Animals
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Endothelium, Vascular / metabolism*
  • Humans
  • Insulin Resistance / genetics*
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / physiology*
  • Signal Transduction / genetics

Substances

  • Receptor, IGF Type 1