Cold exposure induces tissue-specific modulation of the insulin-signalling pathway in Rattus norvegicus

J Physiol. 2003 Oct 1;552(Pt 1):149-62. doi: 10.1113/jphysiol.2003.050369. Epub 2003 Aug 1.


Cold exposure provides a reproducible model of improved glucose turnover accompanied by reduced steady state and glucose-induced insulin levels. In the present report we performed immunoprecipitation and immunoblot studies to evaluate the initial and intermediate steps of the insulin-signalling pathway in white and brown adipose tissues, liver and skeletal muscle of rats exposed to cold. Basal and glucose-induced insulin secretion were significantly impaired, while glucose clearance rates during a glucose tolerance test and the constant for glucose decay during a 15 min insulin tolerance test were increased, indicating a significantly improved glucose turnover and insulin sensitivity in rats exposed to cold. Evaluation of protein levels and insulin-induced tyrosine (insulin receptor, insulin receptor substrates (IRS)-1 and -2, ERK (extracellular signal-related kinase)) or serine (Akt; protein kinase B) phosphorylation of proteins of the insulin signalling cascade revealed a tissue-specific pattern of regulation of the molecular events triggered by insulin such that in white adipose tissue and skeletal muscle an impaired molecular response to insulin was detected, while in brown adipose tissue an enhanced response to insulin was evident. In muscle and white and brown adipose tissues, increased 2-deoxy-D-glucose (2-DG) uptake was detected. Thus, during cold exposure there is a tissue-specific regulation of the insulin-signalling pathway, which seems to favour heat-producing brown adipose tissue. Nevertheless, muscle and white adipose tissue are able to take up large amounts of glucose, even in the face of an apparent molecular resistance to insulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / physiology*
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Cold Temperature*
  • Energy Metabolism / physiology
  • Glucose / metabolism
  • Glucose Transporter Type 4
  • Insulin / metabolism*
  • Insulin Receptor Substrate Proteins
  • Insulin Secretion
  • Liver / metabolism
  • Male
  • Mitogen-Activated Protein Kinases / metabolism
  • Monosaccharide Transport Proteins / metabolism
  • Muscle Proteins*
  • Muscle, Skeletal / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins*
  • Rats
  • Rats, Wistar
  • Signal Transduction / physiology*


  • Glucose Transporter Type 4
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, rat
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Slc2a4 protein, rat
  • Phosphatidylinositol 3-Kinases
  • Akt1 protein, rat
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • Glucose