High insulin levels do not influence PC-1 gene expression and protein content in human muscle tissue and hepatoma cells
✍ Scribed by Lucia Frittitta; Paolo Sbraccia; Benedetta V. Costanzo; Vittorio Tassi; Monica D'Adamo; Daniela Spampinato; Tonino Ercolino; Francesco Purrello; Guido Tamburrano; Riccardo Vigneri; Vincenzo Trischitta
- Book ID
- 101300900
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 124 KB
- Volume
- 16
- Category
- Article
- ISSN
- 1520-7552
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✦ Synopsis
Background To verify whether insulin levels in¯uence 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 speci®c 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 (21.9t4.6 ng/mg protein, 23.8t3.9, 48.0t8.7, respectively). PC-1 protein content was inversely correlated with insulin sensitivity (r=x0.5, 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 signi®cant ( 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 (114t3 vs 102t14 ng/mg protein) in HepG2 cells.
Conclusion
These ®ndings suggest that chronic high insulin levels do not in¯uence PC-1 expression.