The role of IGF-1 resistance in obesity and type 2 diabetes-mellitus-related insulin resistance and vascular disease

Expert Opin Ther Targets. 2010 Dec;14(12):1333-42. doi: 10.1517/14728222.2010.528930.


Importance of the field: The insulin-resistant conditions of type 2 diabetes mellitus (T2DM) and obesity are a major cause of cardiovascular disease on a global scale. These disorders are not only a cause of ill health but are a huge financial drain on healthcare systems. T2DM leads to an increased risk of cardiovascular mortality equivalent to over 10 years of ageing while obesity independent of T2DM also leads to a substantially increased risk of acute myocardial infarction. Recent trials of therapeutic agents and approaches to preventing the cardiovascular complications of type 2 diabetes have been disappointing.

Areas covered in this review: The role of insulin resistance in the endothelium in the regulation of the anti-atherosclerotic signalling molecule NO and a potential important role for IGF-1 in vascular NO production.

What the reader will gain: A comprehensive understanding of how insulin and IGF-1 regulate vascular function and the effect of type 2 diabetes on these pathways.

Take home message: The roles of insulin and IGF-1 in vascular function are complex and intimately related. Nevertheless IGF-1 signalling in the arterial wall has the potential to be manipulated to protect the vasculature against the development of atherosclerosis and its devastating complications.

Publication types

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

MeSH terms

  • Animals
  • Atherosclerosis / complications
  • Atherosclerosis / metabolism*
  • Cardiovascular Diseases* / complications
  • Cardiovascular Diseases* / drug therapy
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Endothelium, Vascular / physiology
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use
  • Insulin Resistance*
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Molecular Targeted Therapy
  • Nitric Oxide / metabolism
  • Obesity* / complications
  • Obesity* / drug therapy
  • Obesity* / etiology
  • Obesity* / metabolism
  • Risk Factors
  • Treatment Outcome
  • Vascular Diseases* / complications
  • Vascular Diseases* / drug therapy


  • Hypoglycemic Agents
  • Insulin
  • Nitric Oxide
  • Insulin-Like Growth Factor I