High insulin levels do not influence PC-1 gene expression and protein content in human muscle tissue and hepatoma cells

Diabetes Metab Res Rev. Jan-Feb 2000;16(1):26-32. doi: 10.1002/(sici)1520-7560(200001/02)16:1<26::aid-dmrr78>3.0.co;2-n.


Background: To verify whether insulin levels influence PC-1 tissue content, we studied PC-1 gene expression and protein content in skeletal muscle of patients with insulinoma, a model of primary hyperinsulinemia. Data were compared with those obtained in matched insulin sensitive or resistant healthy subjects. In addition, the effect of high insulin concentration on PC-1 protein content was studied in HepG2 cells.

Methods: The following measurements were performed: insulin sensitivity by euglycemic clamp; PC-1 protein content and insulin receptor autophosphorylation by specific ELISAs; PC-1 gene expression by competitive polymerase chain reaction (PCR); phosphatidyl-inositol-3 kinase by immunoprecipitation and thin layer chromatography; glycogen synthesis by (14)C-glucose incorporation.

Results: Muscle PC-1 content was similar in the insulinoma patients and in insulin sensitive controls but higher (p<0.01) in insulin resistant controls (21.9+/-4.6 ng/mg protein, 23.8+/-3.9, 48.0+/-8.7, respectively). PC-1 protein content was inversely correlated with insulin sensitivity (r=-0.5, p<0.015) but with neither plasma insulin nor glucose levels. PC-1 protein content was correlated with PC-1 gene expression (r=0.53, p<0.05, n=14). Exposure to high insulin (100 nmol/l for 16 h) caused a significant (p<0.05-0.01) impairment of insulin receptor autophosphorylation, phosphatidyl-inositol-3 kinase activity and glycogen synthesis, but not of PC-1 protein content (114+/-3 vs 102+/-14 ng/mg protein) in HepG2 cells.

Conclusion: These findings suggest that chronic high insulin levels do not influence PC-1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular
  • Gene Expression Regulation*
  • Glucose Clamp Technique
  • Glycogen / biosynthesis
  • Humans
  • Insulin / physiology*
  • Insulin Resistance*
  • Insulinoma / genetics
  • Insulinoma / metabolism*
  • Kinetics
  • Liver Neoplasms
  • Membrane Glycoproteins / genetics*
  • Muscle, Skeletal / metabolism*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoric Diester Hydrolases*
  • Phosphorylation
  • Pyrophosphatases / genetics
  • Receptor, Insulin / metabolism
  • Reference Values
  • Tumor Cells, Cultured


  • Insulin
  • Membrane Glycoproteins
  • Glycogen
  • Phosphatidylinositol 3-Kinases
  • Receptor, Insulin
  • Phosphoric Diester Hydrolases
  • ectonucleotide pyrophosphatase phosphodiesterase 1
  • Pyrophosphatases