Expression of insulin-receptor substrate-1 and -2 in ovaries from women with insulin resistance and from controls

Different phenotypes of polycystic ovary syndrome by Rotterdam criteria are differently steroidogenic but similarly insulin resistant

“…As shown in our study, the three groups of anovulatory PCOS patients had generally normal glucose tolerance during OGTT, but comparable hyperinsulinemia and thus insulin resistance in spite of their different steroidogenesis. Such a contribution of insulin resistance to ovary overactivity and anovulation in our study is in agreement with the traditional Chinese medicine concept that PCOS is a disorder of an ''insulin resistant'' ovary, namely, ''phlegm affected BaoGong (PABG)'' (6,(17)(18)(19). The application of insulin-sensitizing agents in PCOS patients results in improvement in both insulin resistance and ovulation (20,21).…”

Oncogenic Transformation by the Signaling Adaptor Proteins Insulin Receptor Substrate (IRS)-1 and IRS-2

“…[17][18][19][20][21][22][23][24] Originally identified in rat hepatoma cells, 18 IRS-1 has subsequently been found in numerous other tissues expressing IR and/or IGF-IR including brain, muscle, heart, adipocyte, kidney, ovary and mammary gland. [38][39][40][41] Encoded by a single exon on human chromosome 2q36-37 (mouse chromosome 1), it has a molecular weight of 132 kDa, but due to serine phosphorylation it migrates on SDS-polyacrylamide gels with an apparent molecular weight of 185 kDa. 18 We and others have shown that IRS-1 gene transcription can be enhanced by steroids (estrogen and progesterone) in breast cancer cells and in the mouse mammary gland.…”

“…19,25 Similar to the tissue expression of IRS-1, IRS-2 is located in brain, muscle, heart, adipocyte, liver, kidney, ovary and mammary gland. 19,40,41 In addition, like IRS-1, IRS-2 mRNA expression is regulated by steroid hormones. 27 While IRS-1 and IRS-2 are widely expressed, the other members of the IRS family (IRS-3 to IRS-6) show limited species or tissue-restricted expression.…”

Impaired (‘diabetic’) insulin signaling and action occur in fat cells long before glucose intolerance—is insulin resistance initiated in the adipose tissue?

“…9 The impaired tyrosine phosphorylation does not appear to be due to a reduced IRS-1 protein expression, although lower levels have been seen in some cells in gestational diabetes. 10 An increased serine phosphorylation of IRS-1 may reduce the insulin-stimulated tyrosine phosphorylation, 11 but it is currently unknown whether this is the case in type 2 diabetes. Taken together, the data suggest that the activation of PI3-kinase, and presumably the generation of PI3, 4-and PI3, 4, 5 phosphates, is reduced but still sufficient to allow a normal activation of the downstream signaling events.…”