Insulin and the beta3-adrenoceptor differentially regulate uncoupling protein-1 expression

Mol Endocrinol. 2000 Jun;14(6):764-73. doi: 10.1210/mend.14.6.0477.


Cross-talk between insulin and the adrenergic system is important in the regulation of energy homeostasis. In cultured, differentiated mouse brown adipocytes, beta3-adrenergic stimulation induced a 4.5-fold increase in uncoupling protein-1 (UCP-1) expression, which was diminished by 25% in the presence of insulin. Beta3-adrenergic stimulation also activated mitogen-activated protein (MAP) kinase by 3.5-fold and caused a decrease in basal phosphoinositide (PI) 3-kinase activity detected in p110gamma- and Gbeta-subunit-immunoprecipitates in a time-dependent manner, whereas insulin stimulated p110alpha- and phosphotyrosine-associated PI 3-kinase activity. Inhibition of MAP kinase or PI 3-kinase potentiated the beta3-adrenergic effect on UCP-1 expression, both alone and in the presence of insulin. Thus, insulin inhibits beta3-adrenergic stimulation of UCP-1, and both MAP kinase and PI 3-kinase are negative regulatory elements in the beta3-adrenergic control of UCP-1 expression. Cross-talk between the adrenergic and insulin signaling systems and impaired regulation of UCP-1 might contribute to the development of a reduced energy balance, resulting in obesity and insulin resistance.

Publication types

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

MeSH terms

  • Adipocytes / metabolism
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Carrier Proteins / genetics*
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects*
  • Insulin / pharmacology*
  • Ion Channels
  • Membrane Proteins / genetics*
  • Mice
  • Mitochondrial Proteins
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, Adrenergic, beta / physiology*
  • Receptors, Adrenergic, beta-3
  • Signal Transduction
  • Uncoupling Protein 1


  • Carrier Proteins
  • Enzyme Inhibitors
  • Insulin
  • Ion Channels
  • Membrane Proteins
  • Mitochondrial Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-3
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Cyclic AMP-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases