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High insulin levels do not influence PC‐1 gene expression and protein content in human muscle tissue and hepatoma cells
Author(s) -
Frittitta Lucia,
Sbraccia Paolo,
Costanzo Benedetta V.,
Tassi Vittorio,
D'Adamo Monica,
Spampinato Daniela,
Ercolino Tonino,
Purrello Francesco,
Tamburrano Guido,
Vigneri Riccardo,
Trischitta Vincenzo
Publication year - 2000
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/(sici)1520-7560(200001/02)16:1<26::aid-dmrr78>3.0.co;2-n
Subject(s) - insulin , autophosphorylation , medicine , endocrinology , insulin receptor , hyperinsulinemia , insulinoma , gene expression , skeletal muscle , protein kinase a , biology , kinase , chemistry , insulin resistance , gene , biochemistry
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. Copyright © 2000 John Wiley & Sons, Ltd.