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

Lucia Frittitta, Paolo Sbraccia, Benedetta V. Costanzo, Vittorio Tassi, Monica D'Adamo, Daniela Spampinato, Tonino Ercolino, Francesco Purrello, Guido Tamburrano, Riccardo Vigneri, Vincenzo Trischitta

Research output: Contribution to journalArticle

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 14C-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. Copyright (C) 2000 John Wiley and Sons, Ltd.

Original languageEnglish
Pages (from-to)26-32
Number of pages7
JournalDiabetes/Metabolism Research and Reviews
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 2000

Keywords

  • Hyperinsulinemia
  • Insulin receptor tyrosine-kinase activity
  • Insulin resistance
  • Insulinoma
  • PC-1 expression

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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