| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Women's Health, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA
2 Division of Endocrinology, Diabetes and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
3 Division of Diabetes and Endocrine Research, University of California, Mount Zion Medical Center, San Francisco, CA, USA
4 Division of Women's Health, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA; Division of Endocrinology, Diabetes and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
5 Division of Women's Health, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University, The Feinberg School of Medicine, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: a-dunaif{at}northwestern.edu.
Insulin resistance in polycystic ovary syndrome (PCOS) is due to a post-binding defect in
signaling that persists in cultured skin fibroblasts and is associated with constitutive serine
phosphorylation of the insulin receptor (IR). Cultured skeletal muscle from obese women
with PCOS and age- and body mass index (BMI)-matched control women (n = 10/group) was
studied to determine whether signaling defects observed in this tissue in vivo were intrinsic or
acquired. Basal and insulin-stimulated glucose transport and glucose transporter 1 (GLUT1)
abundance were significantly increased in cultured myotubes from women with PCOS.
Neither IR 
-subunit abundance and tyrosine autophosphorylation nor insulin receptor
substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase activity differed in the two
groups. However, IRS-1 protein abundance was significantly increased in PCOS resulting in
significantly decreased PI 3-kinase activity when normalized for IRS-1. Phosphorylation of
IRS-1 on Ser312, a key regulatory site, was significantly increased in PCOS, which may have
contributed to this signaling defect. Insulin signaling via IRS-2 was also decreased in
myotubes from women with PCOS. In summary, decreased insulin-stimulated glucose uptake
in PCOS skeletal muscle in vivo is an acquired defect. Nevertheless, there are intrinsic
abnormalities in glucose transport and insulin signaling in myotubes from affected women,
including increased phosphorylation of IRS-1 Ser312, that may confer increased susceptibility
to insulin resistance-inducing factors in the in vivo environment. These abnormalities differ
from those reported in other insulin resistant states consistent with the hypothesis that PCOS
is a genetically unique disorder conferring an increased risk for type 2 diabetes.
This article has been cited by other articles:
|
|
 |
|
  J. J. Kim, Y. M. Choi, M. A. Hong, S. S. Hwang, S. H. Yoon, S. J. Chae, B. C. Jee, S. Y. Ku, J. G. Kim, and S. Y. Moon Phosphatidylinositol 3-kinase p85{alpha} regulatory subunit gene Met326Ile polymorphism in women with polycystic ovary syndrome Hum. Reprod., May 1, 2009; 24(5): 1184 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. F. Svendsen, L. Nilas, K. Norgaard, J.-E. B. Jensen, and S. Madsbad Obesity, body composition and metabolic disturbances in polycystic ovary syndrome Hum. Reprod., September 1, 2008; 23(9): 2113 - 2121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Franks, J. Stark, and K. Hardy Follicle dynamics and anovulation in polycystic ovary syndrome Hum. Reprod. Update, May 22, 2008; (2008) dmn015v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chakrabarty and M. Nagamani Peripubertal Hyperinsulinemia Upregulates Phosphatidylinositol 3-Kinase/Akt Pathway in Rat Ovaries Reproductive Sciences, March 1, 2008; 15(3): 274 - 284. [Abstract] [PDF]
|
|
|
|
 |
|
 K. Hojlund, D. Glintborg, N. R. Andersen, J. B. Birk, J. T. Treebak, C. Frosig, H. Beck-Nielsen, and J. F.P. Wojtaszewski Impaired Insulin-Stimulated Phosphorylation of Akt and AS160 in Skeletal Muscle of Women With Polycystic Ovary Syndrome Is Reversed by Pioglitazone Treatment Diabetes, February 1, 2008; 57(2): 357 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Skov, D. Glintborg, S. Knudsen, T. Jensen, T. A. Kruse, Q. Tan, K. Brusgaard, H. Beck-Nielsen, and K. Hojlund Reduced Expression of Nuclear-Encoded Genes Involved in Mitochondrial Oxidative Metabolism in Skeletal Muscle of Insulin-Resistant Women With Polycystic Ovary Syndrome Diabetes, September 1, 2007; 56(9): 2349 - 2355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Ma, L. Fan, Y. Meng, Z. Hou, Y.-D. Mao, W. Wang, W. Ding, and J.-Y. Liu Proteomic analysis of human ovaries from normal and polycystic ovarian syndrome Mol. Hum. Reprod., August 1, 2007; 13(8): 527 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.L. Hendriks, J.C.F. Ket, P.G.A. Hompes, R. Homburg, and C.B. Lambalk Why does ovarian surgery in PCOS help? Insight into the endocrine implications of ovarian surgery for ovulation induction in polycystic ovary syndrome Hum. Reprod. Update, May 1, 2007; 13(3): 249 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Beckman, A. B. Goldfine, A. Dunaif, M. Gerhard-Herman, and M. A. Creager Endothelial Function Varies According to Insulin Resistance Disease Type Diabetes Care, May 1, 2007; 30(5): 1226 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Legro A 27-Year-Old Woman With a Diagnosis of Polycystic Ovary Syndrome JAMA, February 7, 2007; 297(5): 509 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Morino, K. F. Petersen, and G. I. Shulman Molecular Mechanisms of Insulin Resistance in Humans and Their Potential Links With Mitochondrial Dysfunction Diabetes, December 1, 2006; 55(Supplement_2): S9 - S15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Gonzalez, N S Rote, J Minium, and J P Kirwan In vitro evidence that hyperglycemia stimulates tumor necrosis factor-{alpha} release in obese women with polycystic ovary syndrome. J. Endocrinol., March 1, 2006; 188(3): 521 - 529. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
