Insulin stimulates the degradation of IRS-1 in 3T3-L1 adipocytes

Biochem Biophys Res Commun. 1993 Feb 15;190(3):961-7. doi: 10.1006/bbrc.1993.1143.

Abstract

One of the first steps that follows insulin receptor activation is the tyrosine phosphorylation of the 160-185 kDa insulin receptor substrate IRS-1. In 3T3-L1 adipocytes, expression of IRS-1 is down-regulated by chronic exposure to insulin. Expression of IRS-1 mRNA is essentially unchanged. However, [35S]Met pulse-chase labeling demonstrates that the rate of degradation of IRS-1 protein is about 10 times faster in insulin-treated cells than in basal cells. The down-regulation occurs in the presence of cycloheximide or actinomycin D and therefore is not dependent upon protein synthesis. Chloroquine does not inhibit the insulin-induced degradation, suggesting that the site of proteolysis is an extra-lysosomal compartment. The insulin-regulated proteolysis of IRS-1 may contribute to the insulin resistance seen in these cells following chronic exposure to insulin.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Adipose Tissue / metabolism*
  • Animals
  • Chloroquine / pharmacology
  • Gene Expression
  • Glucose Transporter Type 4
  • In Vitro Techniques
  • Insulin / pharmacology*
  • Insulin Receptor Substrate Proteins
  • Mice
  • Monosaccharide Transport Proteins / metabolism
  • Muscle Proteins*
  • Phosphatidylinositol 3-Kinases
  • Phosphoproteins / metabolism*
  • Phosphotransferases / metabolism
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Messenger / genetics
  • Transcription, Genetic / drug effects

Substances

  • Glucose Transporter Type 4
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Phosphoproteins
  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Slc2a4 protein, mouse
  • Chloroquine
  • Phosphotransferases
  • Phosphatidylinositol 3-Kinases