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Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome.
J Clin Invest 1995; 96(2):801-10JCI

Abstract

We investigated the cellular mechanisms of the unique disorder of insulin action found in the polycystic ovary syndrome (PCOS). Approximately 50% of PCOS women (PCOS-Ser) had a significant increase in insulin-independent beta-subunit [32P]phosphate incorporation (3.7-fold, P < 0.05 vs other groups) in skin fibroblast insulin receptors that was present in serine residues while insulin-induced tyrosine phosphorylation was decreased (both P < 0.05 vs other groups). PCOS skeletal muscle insulin receptors had the same abnormal phosphorylation pattern. The remaining PCOS women (PCOS-n1) had basal and insulin-stimulated receptor autophosphorylation similar to control. Phosphorylation of the artificial substrate poly GLU4:TYR1 by the PCOS-Ser insulin receptors was significantly decreased (P < 0.05) compared to control and PCOS-n1 receptors. The factor responsible for excessive serine phosphorylation appeared to be extrinsic to the receptor since no insulin receptor gene mutations were identified, immunoprecipitation before autophosphorylation corrected the phosphorylation defect and control insulin receptors mixed with lectin eluates from affected PCOS fibroblasts displayed increased serine phosphorylation. Our findings suggest that increased insulin receptor serine phosphorylation decreases its protein tyrosine kinase activity and is one mechanism for the post-binding defect in insulin action characteristic of PCOS.

Authors+Show Affiliations

Department of Medicine, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey 17033, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7635975

Citation

Dunaif, A, et al. "Excessive Insulin Receptor Serine Phosphorylation in Cultured Fibroblasts and in Skeletal Muscle. a Potential Mechanism for Insulin Resistance in the Polycystic Ovary Syndrome." The Journal of Clinical Investigation, vol. 96, no. 2, 1995, pp. 801-10.
Dunaif A, Xia J, Book CB, et al. Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome. J Clin Invest. 1995;96(2):801-10.
Dunaif, A., Xia, J., Book, C. B., Schenker, E., & Tang, Z. (1995). Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome. The Journal of Clinical Investigation, 96(2), pp. 801-10.
Dunaif A, et al. Excessive Insulin Receptor Serine Phosphorylation in Cultured Fibroblasts and in Skeletal Muscle. a Potential Mechanism for Insulin Resistance in the Polycystic Ovary Syndrome. J Clin Invest. 1995;96(2):801-10. PubMed PMID: 7635975.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome. AU - Dunaif,A, AU - Xia,J, AU - Book,C B, AU - Schenker,E, AU - Tang,Z, PY - 1995/8/1/pubmed PY - 1995/8/1/medline PY - 1995/8/1/entrez SP - 801 EP - 10 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 96 IS - 2 N2 - We investigated the cellular mechanisms of the unique disorder of insulin action found in the polycystic ovary syndrome (PCOS). Approximately 50% of PCOS women (PCOS-Ser) had a significant increase in insulin-independent beta-subunit [32P]phosphate incorporation (3.7-fold, P < 0.05 vs other groups) in skin fibroblast insulin receptors that was present in serine residues while insulin-induced tyrosine phosphorylation was decreased (both P < 0.05 vs other groups). PCOS skeletal muscle insulin receptors had the same abnormal phosphorylation pattern. The remaining PCOS women (PCOS-n1) had basal and insulin-stimulated receptor autophosphorylation similar to control. Phosphorylation of the artificial substrate poly GLU4:TYR1 by the PCOS-Ser insulin receptors was significantly decreased (P < 0.05) compared to control and PCOS-n1 receptors. The factor responsible for excessive serine phosphorylation appeared to be extrinsic to the receptor since no insulin receptor gene mutations were identified, immunoprecipitation before autophosphorylation corrected the phosphorylation defect and control insulin receptors mixed with lectin eluates from affected PCOS fibroblasts displayed increased serine phosphorylation. Our findings suggest that increased insulin receptor serine phosphorylation decreases its protein tyrosine kinase activity and is one mechanism for the post-binding defect in insulin action characteristic of PCOS. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/7635975/Excessive_insulin_receptor_serine_phosphorylation_in_cultured_fibroblasts_and_in_skeletal_muscle__A_potential_mechanism_for_insulin_resistance_in_the_polycystic_ovary_syndrome_ L2 - https://doi.org/10.1172/JCI118126 DB - PRIME DP - Unbound Medicine ER -