Absence of insulin receptor gene mutations in three insulin-resistant women with the polycystic ovary syndrome

Lynn R. Sorbara; Tang Zhichun Tang; Alessandro Cama; Xia Jinru Xia; Esther Schenker; Ronald A. Kohanski; Leonid Poretsky; Elizabeth Koller; Simeon I. Taylor; Andrea Dunaif

doi:10.1016/0026-0495(94)90018-3

Absence of insulin receptor gene mutations in three insulin-resistant women with the polycystic ovary syndrome

Lynn R. Sorbara, Tang Zhichun Tang, Alessandro Cama, Xia Jinru Xia, Esther Schenker, Ronald A. Kohanski, Leonid Poretsky, Elizabeth Koller, Simeon I. Taylor, Andrea Dunaif^*

^*Corresponding author for this work

Medicine, Endocrinology Division

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

Abstract

Women with polycystic ovary syndrome (PCOS) are markedly insulin-resistant, but the molecular mechanisms of these changes and their relationship to the hyperandrogenic state remain to be clarified. Mutations have recently been identified in the insulin receptor gene of patients with extreme forms of insulin resistance associated with hyperandrogenism (eg, type A insulin resistance), and these mutations account for the insulin resistance in such patients. We performed this study to determine whether mutations in the coding portion of the insulin receptor gene were responsible for insulin resistance in PCOS. Insulin binding studies using cultured skin fibroblasts of three obese (body mass index > 27 kg/m²) women with PCOS (ie, mild hyperandrogenemia and chronic anovulation of unknown etiology) and documented insulin resistance showed no apprarent abnormalities in either the number or affinity of insulin binding sites. Direct sequencing of all 22 exons of the insulin receptor gene from two of the women with PCOS did not reveal any mutations. Furthermore, both alleles of the gene were expressed at equal levels. In a third insulin-resistant PCOS woman, there was no evidence for a mutation in the coding portion of the insulin receptor gene as determined by denaturing gradient gel electrophoresis (DGGE). We conclude that the insulin resistance in these PCOS women was caused by a defect extrinsic to the insulin receptor.

Original language	English (US)
Pages (from-to)	1568-1574
Number of pages	7
Journal	Metabolism
Volume	43
Issue number	12
DOIs	https://doi.org/10.1016/0026-0495(94)90018-3
State	Published - Dec 1994

Funding

From the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Pennsylvania State University College of Medicine, Hershey, PA; the Depatiment of Medicine, Division of Endocrinology, and the Department of Biochemisiv, Mt. Sinai School of Medicine, New York, NV; and the National Institute of Diabetes and Digestive and Kidney Diseases, Diabetes Branch, National Institutes of Health, Bethesda. MD. Submitted November 17, 1993; accepted March I, 1994. Supported by grants ffom the National Institutes of Health (ROI DK40605; A.D.), the American Diabetes Association (A.D.), and Phillip Kingsley, Ltd (A.D.). Address reprint requests to Andrea DunaiJ MD, Pennsylvania State University College of Medicine, Division of Endocrinology, Diabetes, and Metabolism, PO Box 8.50, 500 University Dr, Hershey, PA 17033. Copyright 0 I994 by W B. Saunders Company 0026-0495/94/4312-0018$03.OOiO

ASJC Scopus subject areas

Endocrinology
Endocrinology, Diabetes and Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/0026-0495(94)90018-3

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@article{74925ef4678840cd94da14d507a81213,

title = "Absence of insulin receptor gene mutations in three insulin-resistant women with the polycystic ovary syndrome",

abstract = "Women with polycystic ovary syndrome (PCOS) are markedly insulin-resistant, but the molecular mechanisms of these changes and their relationship to the hyperandrogenic state remain to be clarified. Mutations have recently been identified in the insulin receptor gene of patients with extreme forms of insulin resistance associated with hyperandrogenism (eg, type A insulin resistance), and these mutations account for the insulin resistance in such patients. We performed this study to determine whether mutations in the coding portion of the insulin receptor gene were responsible for insulin resistance in PCOS. Insulin binding studies using cultured skin fibroblasts of three obese (body mass index > 27 kg/m2) women with PCOS (ie, mild hyperandrogenemia and chronic anovulation of unknown etiology) and documented insulin resistance showed no apprarent abnormalities in either the number or affinity of insulin binding sites. Direct sequencing of all 22 exons of the insulin receptor gene from two of the women with PCOS did not reveal any mutations. Furthermore, both alleles of the gene were expressed at equal levels. In a third insulin-resistant PCOS woman, there was no evidence for a mutation in the coding portion of the insulin receptor gene as determined by denaturing gradient gel electrophoresis (DGGE). We conclude that the insulin resistance in these PCOS women was caused by a defect extrinsic to the insulin receptor.",

author = "Sorbara, {Lynn R.} and {Zhichun Tang}, Tang and Alessandro Cama and {Jinru Xia}, Xia and Esther Schenker and Kohanski, {Ronald A.} and Leonid Poretsky and Elizabeth Koller and Taylor, {Simeon I.} and Andrea Dunaif",

note = "Funding Information: From the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Pennsylvania State University College of Medicine, Hershey, PA; the Depatiment of Medicine, Division of Endocrinology, and the Department of Biochemisiv, Mt. Sinai School of Medicine, New York, NV; and the National Institute of Diabetes and Digestive and Kidney Diseases, Diabetes Branch, National Institutes of Health, Bethesda. MD. Submitted November 17, 1993; accepted March I, 1994. Supported by grants ffom the National Institutes of Health (ROI DK40605; A.D.), the American Diabetes Association (A.D.), and Phillip Kingsley, Ltd (A.D.). Address reprint requests to Andrea DunaiJ MD, Pennsylvania State University College of Medicine, Division of Endocrinology, Diabetes, and Metabolism, PO Box 8.50, 500 University Dr, Hershey, PA 17033. Copyright 0 I994 by W B. Saunders Company 0026-0495/94/4312-0018$03.OOiO",

year = "1994",

month = dec,

doi = "10.1016/0026-0495(94)90018-3",

language = "English (US)",

volume = "43",

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T1 - Absence of insulin receptor gene mutations in three insulin-resistant women with the polycystic ovary syndrome

AU - Sorbara, Lynn R.

AU - Zhichun Tang, Tang

AU - Cama, Alessandro

AU - Jinru Xia, Xia

AU - Schenker, Esther

AU - Kohanski, Ronald A.

AU - Poretsky, Leonid

AU - Koller, Elizabeth

AU - Taylor, Simeon I.

AU - Dunaif, Andrea

N1 - Funding Information: From the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Pennsylvania State University College of Medicine, Hershey, PA; the Depatiment of Medicine, Division of Endocrinology, and the Department of Biochemisiv, Mt. Sinai School of Medicine, New York, NV; and the National Institute of Diabetes and Digestive and Kidney Diseases, Diabetes Branch, National Institutes of Health, Bethesda. MD. Submitted November 17, 1993; accepted March I, 1994. Supported by grants ffom the National Institutes of Health (ROI DK40605; A.D.), the American Diabetes Association (A.D.), and Phillip Kingsley, Ltd (A.D.). Address reprint requests to Andrea DunaiJ MD, Pennsylvania State University College of Medicine, Division of Endocrinology, Diabetes, and Metabolism, PO Box 8.50, 500 University Dr, Hershey, PA 17033. Copyright 0 I994 by W B. Saunders Company 0026-0495/94/4312-0018$03.OOiO

PY - 1994/12

Y1 - 1994/12

N2 - Women with polycystic ovary syndrome (PCOS) are markedly insulin-resistant, but the molecular mechanisms of these changes and their relationship to the hyperandrogenic state remain to be clarified. Mutations have recently been identified in the insulin receptor gene of patients with extreme forms of insulin resistance associated with hyperandrogenism (eg, type A insulin resistance), and these mutations account for the insulin resistance in such patients. We performed this study to determine whether mutations in the coding portion of the insulin receptor gene were responsible for insulin resistance in PCOS. Insulin binding studies using cultured skin fibroblasts of three obese (body mass index > 27 kg/m2) women with PCOS (ie, mild hyperandrogenemia and chronic anovulation of unknown etiology) and documented insulin resistance showed no apprarent abnormalities in either the number or affinity of insulin binding sites. Direct sequencing of all 22 exons of the insulin receptor gene from two of the women with PCOS did not reveal any mutations. Furthermore, both alleles of the gene were expressed at equal levels. In a third insulin-resistant PCOS woman, there was no evidence for a mutation in the coding portion of the insulin receptor gene as determined by denaturing gradient gel electrophoresis (DGGE). We conclude that the insulin resistance in these PCOS women was caused by a defect extrinsic to the insulin receptor.

AB - Women with polycystic ovary syndrome (PCOS) are markedly insulin-resistant, but the molecular mechanisms of these changes and their relationship to the hyperandrogenic state remain to be clarified. Mutations have recently been identified in the insulin receptor gene of patients with extreme forms of insulin resistance associated with hyperandrogenism (eg, type A insulin resistance), and these mutations account for the insulin resistance in such patients. We performed this study to determine whether mutations in the coding portion of the insulin receptor gene were responsible for insulin resistance in PCOS. Insulin binding studies using cultured skin fibroblasts of three obese (body mass index > 27 kg/m2) women with PCOS (ie, mild hyperandrogenemia and chronic anovulation of unknown etiology) and documented insulin resistance showed no apprarent abnormalities in either the number or affinity of insulin binding sites. Direct sequencing of all 22 exons of the insulin receptor gene from two of the women with PCOS did not reveal any mutations. Furthermore, both alleles of the gene were expressed at equal levels. In a third insulin-resistant PCOS woman, there was no evidence for a mutation in the coding portion of the insulin receptor gene as determined by denaturing gradient gel electrophoresis (DGGE). We conclude that the insulin resistance in these PCOS women was caused by a defect extrinsic to the insulin receptor.

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ER -

Absence of insulin receptor gene mutations in three insulin-resistant women with the polycystic ovary syndrome

Abstract

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ASJC Scopus subject areas

UN SDGs

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