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

Abstract

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.

• Authors: L Frittitta, P Sbraccia, B V Costanzo, V Tassi, M D'Adamo, D Spampinato, T Ercolino, F Purrello, G Tamburrano, R Vigneri, V Trischitta
• Journal: Diabetes/metabolism research and reviews (Diabetes Metab Res Rev) 2000 Jan-Feb Vol. 16 Issue 1 Pg. 26-32 ISSN: 1520-7552 [Print] England
• PMID: 10707036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 John Wiley & Sons, Ltd.

Chemical References

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

Topics

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