Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue

Alex W. Cohen, Babak Razani, Xiao Bo Wang, Terry P. Combs, Terence M. Williams, Philipp E. Scherer, Michael P. Lisanti

Research output: Contribution to journalArticlepeer-review

284 Scopus citations


Several lines of evidence suggest that a functional relationship exists between caveolin-1 and insulin signaling. However, it remains unknown whether caveolin-1 is normally required for proper insulin receptor signaling in vivo. To address this issue, we examined the status of insulin receptor signaling in caveolin-1 (-/-)-deficient (Cav-1 null) mice. Here, we show that Cav-1 null mice placed on a high-fat diet for 9 mo develop postprandial hyperinsulinemia. An insulin tolerance test (ITT) revealed that young Cav-1 null mice on a normal chow diet are significantly unresponsive to insulin, compared with their wild-type counterparts. This insulin resistance is due to a primary defect in adipose tissue, as evidenced by drastically reduced insulin receptor protein levels (>90%), without any changes in insulin receptor mRNA levels. These data suggest that caveolin-1 acts as a molecular chaperone that is necessary for the proper stabilization of the insulin receptor in adipocytes in vivo. In support of this notion, we demonstrate that recombinant expression of caveolin-1 in Cav-1 null mouse embryo fibroblasts rescues insulin receptor protein expression. These data provide evidence that the lean body phenotype observed in the Cav-1 knockout mice is due, at least in part, to a defect in insulin-regulated lipogenesis.

Original languageEnglish (US)
Pages (from-to)C222-C235
JournalAmerican Journal of Physiology - Cell Physiology
Issue number1 54-1
StatePublished - Jul 1 2003


  • Caveolae
  • Caveolin
  • Insulin signaling
  • Knockout mice
  • Protein stabilization

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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