Brown adipose tissue-specific insulin receptor knockout shows diabetic phenotype without insulin resistance

J Clin Invest. 2001 Oct;108(8):1205-13. doi: 10.1172/JCI13103.


Although insulin regulates metabolism in both brown and white adipocytes, the role of these tissues in energy storage and utilization is quite different. Recombination technology using the Cre-loxP approach allows inactivation of the insulin receptor in a tissue-specific manner. Mice lacking insulin receptors in brown adipocytes show an age-dependent loss of interscapular brown fat but increased expression of uncoupling protein-1 and -2. In parallel, these mice develop an insulin-secretion defect resulting in a progressive glucose intolerance, without insulin resistance. This model provides direct evidence for not only a role for the insulin receptors in brown fat adipogenesis, the data also suggest a novel role of brown adipose tissue in the regulation of insulin secretion and glucose homeostasis.

Publication types

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

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Insulin / metabolism
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology*
  • Insulin Secretion
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Phenotype
  • RNA / genetics
  • RNA / metabolism
  • Receptor, Insulin / genetics*
  • Receptor, Insulin / metabolism*
  • Signal Transduction
  • Tissue Distribution


  • Insulin
  • RNA
  • Receptor, Insulin