Insulin signalling and the regulation of glucose and lipid metabolism

Nature. 2001 Dec 13;414(6865):799-806. doi: 10.1038/414799a.


The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells. But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes.

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Cytoskeletal Proteins / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucose / metabolism*
  • Insulin / metabolism*
  • Insulin Resistance
  • Lipid Metabolism*
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-cbl
  • Receptor, Insulin / metabolism
  • Signal Transduction*
  • Ubiquitin-Protein Ligases*


  • Cytoskeletal Proteins
  • Insulin
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-cbl
  • Ubiquitin-Protein Ligases
  • Phosphatidylinositol 3-Kinases
  • Receptor, Insulin
  • Cbl protein, mouse
  • Glucose