The adipose cell lineage is not intrinsically insulin resistant in polycystic ovary syndrome.
Selective resistance to the effects of insulin on glucose metabolism in skeletal muscle and adipose tissue is a key feature of polycystic ovary syndrome (PCOS). The pathogenesis of insulin resistance in skeletal muscle in PCOS involves interaction of in vivo environmental factors with intrinsic defects in insulin signaling. We aimed to determine whether (1) intrinsic defects in insulin action/signaling and cytokine secretion were present in adipose cells in PCOS and (2) insulin resistance can be induced in control adipose cells by culture in medium conditioned by insulin-resistant PCOS fibroblasts. Subcutaneous abdominal preadipocytes from obese women with PCOS (n = 7) and age- and body mass index-matched controls (n = 5) were cultured for several generations in vitro. Basal and insulin-stimulated glycogen synthesis and basal glucose transport did not differ in the preadipocytes from women with PCOS and controls. Abundance of insulin receptor (IR) beta subunit, insulin receptor substrate (IRS) 1 and 2, p85 subunit of phosphatidylinositol 3-kinase, and extracellular signal-regulated kinase (ERK)1/2 activation did not differ. Secretion of tumor necrosis factor alpha and interleukin 6 did not differ. Insulin action on glycogen synthesis in control preadipocytes was not altered by coculture with or growth in media conditioned by PCOS skin fibroblasts with constitutive serine phosphorylation of IRbeta subunit (IR ser+), indicating that IR ser+ cells do not secrete an insulin resistance-inducing factor. We conclude that in contrast to skeletal muscle and skin fibroblasts, there is no evidence for intrinsic defects in insulin signaling in the PCOS adipose cell lineage, indicating that insulin resistance in these cells is likely due to factors in the in vivo environment.
Corbould
Anne
A
Division of Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. anne.corbould@princehenrys.org
Dunaif
Andrea
A
D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D019070:Cell Lineage; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000378:metabolism* / Q000473:pathology; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D051246:Glucose Transport Proteins, Facilitative; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha; D006003:Glycogen; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D048049:Extracellular Signal-Regulated MAP Kinases