Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Research on insulin action in PCOS has been intensive after the identification of insulin resistance as a feature of the syndrome in 1980. It is now clear that PCOS is a metabolic as well as a reproductive disorder and an important cause of type 2 diabetes mellitus in women. The cellular and molecular mechanisms of insulin resistance in PCOS are distinct from those in other insulin resistance syndromes. Elucidating these mechanisms promises to provide considerable insight into insulin receptor signal specificity. Conversely, insulin resistance is now known to have an important role in the pathogenesis of the reproductive disturbances of PCOS. It is thought that one or several genetic defects may cause both the insulin resistance and reproductive abnormalities characteristic of PCOS.
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PMID:Insulin action in the polycystic ovary syndrome. 1035 22

Polycystic ovary syndrome is a reproductive disorder with a significant impact on fertility. It is secondarily, and perhaps for the individual primarily, a disorder with a marked increase risk for diabetes and glucose intolerance. Physicians need to be aware that women who have PCOS are at high risk for impaired glucose tolerance and type 2 diabetes. In the author's opinion, they should be screened for these abnormalities. Minority women with PCOS may have higher prevalence rates of glucose intolerance, and further study of minority groups is indicated. The author's data indicate that fasting glucose levels are inadequate for such screenings. Fasting glucose levels are relatively poor predictors of type 2 diabetes as determined by glucose challenge testing in PCOS. These findings may have substantial clinical relevance. They strongly suggest that all PCOS women should be screened for glucose intolerance, and that basal and 2-hour, glucose-stimulated levels rather than fasting glucose levels alone are required for such screening. Further study is necessary to document conversion rates to worsening glucose tolerance over time, as well as the cardiovascular risk associated with glucose intolerance in PCOS.
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PMID:Diabetes prevalence and risk factors in polycystic ovary syndrome. 1129 7

Polycystic ovary syndrome (PCOS) is now recognized as an important metabolic and reproductive disorder. It is associated with substantial defects in insulin action and secretion that confer a markedly increased risk for type 2 diabetes mellitus. Insulin resistance modifies reproductive function both by the direct actions of insulin on steroidogenesis and by disruption of insulin signaling pathways in the central nervous system. These insights have led to a new therapy for PCOS with insulin-sensitizing agents. Hyperandrogenemia and insulin resistance cluster in PCOS families, consistent with a genetic susceptibility to these abnormalities. There is evidence for both linkage and association of the hyperandrogenemia phenotype with an allele of a marker locus on chromosome 19, in the region of the gene encoding the insulin receptor.
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PMID:Polycystic ovary syndrome: syndrome XX? 1451 34

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5-10% of reproductive aged women, about 1 out of 15 women worldwide. Traditionally it was considered as a reproductive disorder showing hyperandrogenism, chronic anovulation and infertility; it is now well accepted that PCOS represents a ''multifaceted'' syndrome with substantial metabolic and cardiovascular long term consequences. Several PCOS women present abdominal adiposity (visceral fat) with a level of peripheral insulin resistance (IR), similar to that present in women with type 2 diabetes, in association with an increased incidence of impaired glucose tolerance. Several cardiovascular risk factors are often related to metabolic alterations, such as dyslipidemia, hypertension, endothelial dysfunction, low grade chronic inflammation, that are present even at early age in PCOS women. Pathogenetic mechanisms of these impairments are not completely clarified yet, but IR appears to play a critical role, such as the key factor linking hypertension, glucose intolerance, obesity, lipid abnormalities and coronary artery disease. In conclusion, although increased incidence of metabolic abnormalities and metabolic disease like type 2 diabetes, and several cardiovascular abnormalities have been widely demonstrated in PCOS women, larger and multicenter trials of long term cardiovascular outcomes are required to better define the incidence of cardiovascular risk and cardiovascular disease in PCOS.
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PMID:Metabolic and cardiovascular consequences of polycystic ovary syndrome. 1827 51

Polycystic ovary syndrome (PCOS) is now recognized as an important metabolic as well as reproductive disorder conferring substantially increased risk for type 2 diabetes. Affected women have marked insulin resistance, independent of obesity. This article summarizes the state of the science since we last reviewed the field in the Endocrine Reviews in 1997. There is general agreement that obese women with PCOS are insulin resistant, but some groups of lean affected women may have normal insulin sensitivity. There is a post-binding defect in receptor signaling likely due to increased receptor and insulin receptor substrate-1 serine phosphorylation that selectively affects metabolic but not mitogenic pathways in classic insulin target tissues and in the ovary. Constitutive activation of serine kinases in the MAPK-ERK pathway may contribute to resistance to insulin's metabolic actions in skeletal muscle. Insulin functions as a co-gonadotropin through its cognate receptor to modulate ovarian steroidogenesis. Genetic disruption of insulin signaling in the brain has indicated that this pathway is important for ovulation and body weight regulation. These insights have been directly translated into a novel therapy for PCOS with insulin-sensitizing drugs. Furthermore, androgens contribute to insulin resistance in PCOS. PCOS may also have developmental origins due to androgen exposure at critical periods or to intrauterine growth restriction. PCOS is a complex genetic disease, and first-degree relatives have reproductive and metabolic phenotypes. Several PCOS genetic susceptibility loci have been mapped and replicated. Some of the same susceptibility genes contribute to disease risk in Chinese and European PCOS populations, suggesting that PCOS is an ancient trait.
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PMID:Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. 2306 22

Polycystic ovary syndrome (PCOS) is a widespread reproductive disorder that encompasses many associated health conditions and has an impact on various metabolic processes. PCOS is depicted by hyperandrogenism, polycystic ovaries, and anovulation. It increases the risk of insulin resistance (IR), type 2 diabetes, obesity, and cardiovascular disease. The etiology of the disease remains unclear, and the subjective phenotype makes a united diagnosis difficult among physicians. It seems to be a familial genetic syndrome caused by a combination of environmental and genetic factors. It can be linked with metabolic disorders in first-degree family members. PCOS is the cause of up to 30% of infertility in couples seeking treatment. Currently, there is no cure for PCOS. Despite the growing incidence of this syndrome, limited research has been done that encompasses the entirety of PCOS spectrum. In this review, the current status and possible future perspective will be discussed.
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PMID:Polycystic ovary syndrome: current status and future perspective. 2438 46

Polycystic ovary syndrome is the most common endocrine disorder among women of reproductive age. Although traditionally viewed as a reproductive disorder, there is increasing appreciation that it is associated with significantly increased risk of cardiometabolic disorders. Women with polycystic ovary syndrome may present to clinicians via a variety of different routes and symptoms. Although the impact on reproduction predominates during the reproductive years, the increased cardiometabolic problems are likely to become more important at later stages of the life course. Women with polycystic ovary syndrome have an approximately 2- to 5-fold increased risk of dysglycaemia or type 2 diabetes, and hence regular screening with oral glucose tolerance test is warranted. Although the diagnostic criteria for polycystic ovary syndrome are still evolving and are undergoing revision, the diagnosis is increasingly focused on the presence of hyperandrogenism, with the significance of polycystic ovarian morphology in the absence of associated hyperandrogenism or anovulation remaining uncertain. The management of women with polycystic ovary syndrome should focus on the specific needs of the individual, and may change according to different stages of the life course. In view of the clinical manifestations of the condition, there is recent debate about whether the current name is misleading, and whether the condition should be renamed as metabolic reproductive syndrome.
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PMID:Polycystic ovary syndrome: a common reproductive syndrome with long-term metabolic consequences. 2917 Mar 61

Polycystic ovary syndrome (PCOS) is a common metabolic and reproductive disorder with an increasing risk for type 2 diabetes. Insulin resistance is a common feature of women with PCOS, but the underlying molecular mechanism remains unclear. This study aimed to screen critical long non-coding RNAs (lncRNAs) that might play pivotal roles in insulin resistance, which could provide candidate biomarkers and potential therapeutic targets for PCOS. Gene expression profiles of the skeletal muscle in patients with PCOS accompanied by insulin resistance and healthy patients were obtained from the publicly available Gene Expression Omnibus (GEO) database. A global triple network including RNA-binding protein, mRNA, and lncRNAs was constructed based on the data from starBase. Then, we extracted an insulin resistance-associated lncRNA-mRNA network (IRLMN) by integrating the data from starBase and GEO. We also performed a weighted gene co-expression network analysis (WGCNA) on the differentially expressed genes between the women with and without PCOS, to identify hub lncRNAs. Additionally, the findings of key lncRNAs were examined in an independent GEO dataset. The expression level of lncRNA RP11-151A6.4 in ovarian granulosa cells was increased in patients with PCOS compared with that in control women. Levels were also increased in PCOS patients with higher BMI, hyperinsulinemia, and higher HOMA-IR values. As a result, RP11-151A6.4 was identified as a hub lncRNA based on IRLMN and WGCNA and was highly expressed in ovarian granulosa cells, skeletal muscle, and subcutaneous and omental adipose tissues of patients with insulin resistance. This study showed the differences between lncRNA and mRNA profiles from healthy women and women with PCOS and insulin resistance. Here, we demonstrated that RP11-151A6.4 might play a vital role in insulin resistance, androgen excess, and adipose dysfunction in patients with PCOS. Further study concerning RP11-151A6.4 could elucidate the underlying mechanisms of insulin resistance.
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PMID:Polycystic Ovary Syndrome: Novel and Hub lncRNAs in the Insulin Resistance-Associated lncRNA-mRNA Network. 3150 35

Polycystic ovary syndrome (PCOS) has been traditionally perceived as a reproductive disorder due to its most common presentation with menstrual dysfunction and infertility. However, it is now clear that women with PCOS are at increased risk of metabolic dysfunction, from impaired glucose tolerance and type 2 diabetes mellitus to nonalcoholic fatty liver disease and cardiovascular disease. PCOS is characterised by androgen excess, with cross-sectional data showing that hyperandrogenism is directly complicit in the development of metabolic complications. Recent studies have also shown that C11-oxy C19 androgens are emerging to be clinically and biochemically significant in PCOS, thus emphasising the importance of understanding the impact of both classic and C11-oxy C19 androgens on women's health. Here we discuss androgen metabolism in the context of PCOS, and dissect the role played by androgens in the development of metabolic disease through their effects on metabolic target tissues in women.
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PMID:Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome. 3263 65