Mechanisms for insulin resistance: common threads and missing links

Cell. 2012 Mar 2;148(5):852-71. doi: 10.1016/j.cell.2012.02.017.


Insulin resistance is a complex metabolic disorder that defies explanation by a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway, and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, these cellular changes may converge to promote the accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, a common final pathway leading to impaired insulin signaling and insulin resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / metabolism
  • Diet
  • Endoplasmic Reticulum Stress
  • Fatty Liver / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Lipid Metabolism*
  • Liver / pathology
  • Muscle, Skeletal / metabolism
  • Non-alcoholic Fatty Liver Disease
  • Signal Transduction
  • Unfolded Protein Response


  • Insulin