Enhanced mitogenic signaling in skeletal muscle of women with polycystic ovary syndrome

Diabetes
A CorbouldA Dunaif

Abstract

Insulin resistance in polycystic ovary syndrome (PCOS) results from a postbinding defect in signaling. Insulin receptor and insulin receptor substrate (IRS)-1 serine hyperphosphorylation by an unidentified kinase(s) contributes to this defect. We investigated whether insulin resistance is selective, affecting metabolic but not mitogenic pathways, in skeletal muscle as it is in cultured skin fibroblasts in PCOS. Extracellular signal-regulated kinase (ERK)1/2 activation was increased in skeletal muscle tissue and in cultured myotubes basally and in response to insulin in women with PCOS compared with control women. Mitogen-activated/extracellular signal-regulated kinase kinase (MEK)1/2 was also activated in PCOS, whereas p38 mitogen-activated protein kinase phosphorylation and signaling from the insulin receptor to Grb2 was similar in both groups. The activity of p21Ras was decreased and Raf-1 abundance increased in PCOS, suggesting that altered mitogenic signaling began at this level. MEK1/2 inhibition reduced IRS-1 Ser312 phosphorylation and increased IRS-1 association with the p85 subunit of phosphatidylinositol 3-kinase in both groups. We conclude that in PCOS skeletal muscle, 1) mitogenic signaling is enhanced in vivo and in...Continue Reading

References

Oct 1, 1996·Molecular and Cellular Biology·H MischakW Kolch
Dec 24, 1997·Current Topics in Microbiology and Immunology·M F White, L Yenush
Jul 11, 1998·The Journal of Biological Chemistry·M F FavataJ M Trzaskos
Apr 9, 1999·The Journal of Clinical Investigation·A VirkamäkiC R Kahn
Jun 4, 1999·Progress in Biophysics and Molecular Biology·M H Cobb
Feb 17, 2000·The Journal of Clinical Investigation·K CusiL J Mandarino
Jul 7, 2001·American Journal of Physiology. Endocrinology and Metabolism·A DunaifE Diamanti-Kandarakis
Nov 15, 2001·The Journal of Biological Chemistry·Monica MontagnaniBoris Draznin
Sep 28, 2002·The Journal of Biological Chemistry·Zhanguo GaoJianping Ye
Jan 3, 2003·The Journal of Biological Chemistry·Michael W GreeneRichard A Roth
Dec 23, 2004·American Journal of Physiology. Endocrinology and Metabolism·Anne CorbouldAndrea Dunaif

❮ Previous
Next ❯

Citations

Jan 31, 2008·Expert Reviews in Molecular Medicine·Evanthia Diamanti-Kandarakis
Feb 6, 2008·Nature Clinical Practice. Endocrinology & Metabolism·Leslie K Hoffman, David A Ehrmann
Oct 23, 2013·Nature Reviews. Endocrinology·Sara Della TorreAdriana Maggi
Jan 9, 2008·Seminars in Reproductive Medicine·Pinar H Kodaman, Antoni J Duleba
Oct 14, 2010·Metabolic Syndrome and Related Disorders·Andrew A Bremer
Sep 14, 2010·Human Reproduction Update·Cheryce L HarrisonHelena J Teede
Jun 12, 2008·American Journal of Physiology. Endocrinology and Metabolism·Marek DemissieJon E Levine
Feb 26, 2009·American Journal of Physiology. Endocrinology and Metabolism·Xianling LiuFeng Liu
Feb 10, 2011·Annals of Nutrition & Metabolism·Sergio Muntoni, Sandro Muntoni
Jan 20, 2011·The Journal of Clinical Investigation·Cheryl J ParkJon E Levine
Oct 11, 2008·BMC Neuroscience·Christian HolscherCalum Sutherland
Feb 22, 2013·The Journal of Endocrinology·Xiaonan YanJiayin Liu
Dec 22, 2010·The Journal of Endocrinology·Milos LazicAndrea Dunaif
Jan 30, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Snežana TepavčevićGoran Korićanac
Dec 5, 2012·ISRN Endocrinology·Edoardo Mannucci
Sep 16, 2011·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Annu MakkerAnjoo Agarwal
Aug 19, 2009·Nursing for Women's Health·Elizabeth Mary DuRantElizabeth A Critch
Mar 20, 2012·Metabolism: Clinical and Experimental·Kevin B ComerfordSidika E Karakas
Jul 11, 2009·Fertility and Sterility·Henry BohlerStephen J Winters
Aug 2, 2008·Fertility and Sterility·JunWei QuRisto Erkkola
Jul 29, 2008·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·Aldo GalluzzoCarla Giordano
Mar 20, 2010·Journal of Biomedicine & Biotechnology·Melpomeni PeppaSotirios A Raptis
Apr 21, 2007·Metabolism: Clinical and Experimental·Anne Corbould, Andrea Dunaif
Sep 29, 2011·Diabetic Medicine : a Journal of the British Diabetic Association·J M PauliR S Legro
May 21, 2014·Journal of Diabetes Investigation·Hiroshi NotoMitsuhiko Noda
Sep 16, 2010·The FEBS Journal·Suresh MishraB L Grégoire Nyomba
Nov 21, 2015·Medicine and Science in Sports and Exercise·Gislaine Satyko KogureRosana Maria Dos Reis
Aug 22, 2015·Journal of Endocrinological Investigation·M C AmatoC Giordano
Mar 12, 2013·ISRN Oncology·Samy L Habib, Maciej Rojna
Apr 14, 2016·The Journal of Obstetrics and Gynaecology Research·Enes BilSerdar Dilbaz
Jul 1, 2015·International Journal of Endocrinology·Dinka Pavicic BaldaniRoya Ougouag

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

American Diabetes Association Journals

Discover the latest diabetes research published by the journals from the American Diabetes Association.