Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The peroxisome proliferator-activated receptors (PPARs) are a group of three nuclear receptor isoforms, PPAR gamma, PPAR alpha, and PPAR delta, encoded by different genes. PPARs are ligand-regulated transcription factors that control gene expression by binding to specific response elements (PPREs) within promoters. PPARs bind as heterodimers with a retinoid X receptor and, upon binding agonist, interact with cofactors such that the rate of transcription initiation is increased. The PPARs play a critical physiological role as lipid sensors and regulators of lipid metabolism. Fatty acids and eicosanoids have been identified as natural ligands for the PPARs. More potent synthetic PPAR ligands, including the fibrates and thiazolidinediones, have proven effective in the treatment of dyslipidemia and diabetes. Use of such ligands has allowed researchers to unveil many potential roles for the PPARs in pathological states including atherosclerosis, inflammation, cancer, infertility, and demyelination. Here, we present the current state of knowledge regarding the molecular mechanisms of PPAR action and the involvement of the PPARs in the etiology and treatment of several chronic diseases.
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PMID:The mechanisms of action of PPARs. 1181 83

A cohort of 786 women who received a diagnosis of polycystic ovary syndrome (PCOS) in the United Kingdom before 1979 was traced to investigate the long-term consequences of the syndrome. Data were obtained from death certificates for 70 women. Morbidity data were collected from general practice records and questionnaires for 319 women diagnosed with PCOS an average of 31 years previously and for 1060 age-matched control women. The proportion of women with involuntary infertility was 17.5% in the PCOS group compared with 1.3% in the control group. All-cause mortality in the cohort did not differ from that of the general population of women. Women with PCOS were not at significantly increased risk of mortality or morbidity from breast cancer but were at increased risk of endometrial cancer. Women with a history of PCOS had higher levels of several cardiovascular risk factors including diabetes, hypertension, raised plasma cholesterol and body mass index > 30 kg m(minus sign2). Mortality and morbidity from coronary heart disease did not differ significantly between the women with PCOS and comparison groups. Control of obesity is likely to be particularly important for women with a history of PCOS.
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PMID:Long-term consequences of polycystic ovary syndrome: results of a 31 year follow-up study. 1184 63

From ancient times, Swarnabhasma (gold ash) has been used in several clinical manifestations including loss of memory, defective eyesight, infertility, overall body weakness and incidence of early aging. Swarnabhasma has been used by Ayurvedic physicians to treat different diseases like bronchial asthma, rheumatoid arthritis, diabetes mellitus, nervous disorders, etc. In the present investigation, Swarnabhasma was prepared after proper purification and calcination as per Ayurvedic pharmacy which consisted of Realger (As(2)S(2)), Lead oxide (Pb(3)O(4)), Pure gold (Au) and Latex of Calotropis gigantea. Qualitative analyses indicated that Swarnabhasma contained not only gold but also several microelements (Fe, Al, Cu, Zn, Co, Mg, Ca, As, Pb, etc.). Infrared spectroscopy showed that the material was free from any organic compound. The metal content in the bhasma was determined by atomic absorption spectrometry. Acute oral administration of Swarnabhasma showed no mortality in mice (up to 1 ml /20 g b.w. of Swarnabhasma suspension containing 1mg of drug). Chronic administration of Swarnabhasma also showed no toxicity as judged by SGPT, SGOT, serum creatinine and serum urea level and histological studies. In an experimental animal model, chronic Swarnabhasma-treated animals showed significantly increased superoxide dismutase and catalase activity, two enzymes that reduce free radical concentrations in the body.
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PMID:Evaluation of chemical constituents and free-radical scavenging activity of Swarnabhasma (gold ash), an ayurvedic drug. 1200 4

Vascular endothelial growth factor (VEGF) is a potent stimulator of vascular proliferation and permeability. Ovarian granulosa cells have been identified as a major source of the cytokine and r-hCG was able to stimulate VEGF mRNA expression in vitro. In this study we have investigated the immediate effect of ovulation induction with hCG on peripheral VEGF levels in 6 women with primary infertility enrolled in the IVF/ET program. The patients underwent a 24-hour continuous blood withdrawal with sampling intervals of 15 minutes starting from 5 hours before ovulation induction with 10.000 IU hCG. Ovulation induction with hCG had no significant immediate effect on mean peripheral VEGF levels. However, VEGF plasma levels did exhibit significant episodic fluctuations with rapid increases every 90-120 minutes without any relation to circulating hCG levels. Taken together, the results of this study suggest that VEGF is released episodically and that systemic VEGF levels are not acutely altered by ovulation induction with hCG.
Exp Clin Endocrinol Diabetes 2002 May
PMID:VEGF plasma pattern in ovulation induction: evidence for an episodic secretion and lack of immediate effect of hCG. 1201 73

Obesity, the result of combined genetic and environmental factors, is in recent decades one of the most frequent diseases and is encountered mainly in Europe and North America. In women it is associated with the risk of several diseases, such as diabetes mellitus, osteoarthritis, cardiovascular diseases, sleep apnoea syndromee, breast cancer, cancer of the uterus and also with impairment of reproductive functions. Already during the last century some observations confirmed that a very low or very high body weight is more frequently associated with disorders of the menstrual cycle (MC), infertility and poor reproductive capacity. However only during the last decades the pathophysiological and molecular mechanisms of this relationship were gradually elucidated. The main factors which influences the menstrual cycle in obesity are: impaired estrogen metabolism, changes in the concentration of sex hormone binding globulin, hyperinsulinaemia, and probably also leptin levels.
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PMID:[Obesity and disorders of the menstrual cycle]. 1206 Nov 86

A critical step in ovarian biology is the transition of the developmentally arrested primordial follicle to the growing primary follicle. The current study utilizes a rat ovarian organ culture system to investigate the role of insulin and insulin-like growth factor-1 (IGF-1) in this process. Four-day-old rat ovaries were cultured and the degree of primordial to primary follicle transition measured. Insulin increased the primordial to primary follicle transition 30% over control with a half maximal effective concentration (EC50) between 2.5 and 5 ng/ml. IGF-1 did not cause an increase in the primordial to primary follicle transition at concentrations up to 100 ng/ml. Ovaries were also treated with epidermal growth factor (EGF) and hepatocyte growth factor (HGF) and neither had an effect on the primordial to primary follicle transition. Ovaries were treated with insulin in conjunction with other factors known to promote the primordial to primary follicle transition in order to discern any potential synergistic effects. Previous experiments have shown that kit ligand (KL), basic fibroblast growth factor (bFGF) and leukemia inhibitory factor (LIF) promote the primordial to primary follicle transition. Insulin was shown to have an additive effect with KL and LIF, but not bFGF. The fact that insulin can influence the primordial to primary follicle transition at low concentrations (i.e. 5 ng/ml) and that IGF-1 has no effect suggests that insulin is acting at the insulin receptor, not the IGF-1 receptor. The observation that insulin has an additive effect with KL and LIF, but not bFGF, suggests the insulin's site of action is likely the oocyte. In summary, observations suggest that insulin acts as an endocrine type factor to help coordinate primordial to primary follicle transition at the level of the oocyte. The significance of the observations in relation to diabetes and female infertility is discussed.
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PMID:Insulin but not insulin-like growth factor-1 promotes the primordial to primary follicle transition. 1208 65

Polycystic ovary syndrome (PCOS) is a common endocrine condition with reproductive and metabolic consequences, including anovulation, infertility and an increased prevalence of diabetes mellitus. Obesity, central obesity and insulin resistance are strongly implicated in its etiology and reduction of these risk factors should be a central treatment focus. Short-term weight loss has been consistently successful in reducing insulin resistance and restoring ovulation and fertility. However, problems arise with maintaining weight loss and precisely quantifying the associated long-term benefits of risk factor change. Although recent research indicates modest long-term lifestyle changes might reduce the extent of impaired glucose tolerance and delay the conversion to diabetes mellitus in the general population, this has not yet been examined in women with PCOS. Current conservative treatment should emphasize sustainable weight loss through dietary modification and exercise. Modifying additional lifestyle factors, including alcohol consumption, psychosocial stressors and smoking, are also crucial in long-term treatment of PCOS.
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PMID:The role of lifestyle modification in polycystic ovary syndrome. 1212 86

Early diagnosis and therapy of the underlying insulin resistance of heritable polycystic ovary syndrome (PCOS), often manifested at menarche, facilitate the reduction and/or reversal of the reproductive and metabolic morbidity of PCOS, as well as reduce the risk factors for cardiovascular disease. PCOS is characterised by oligoamenorrhoea, clinical and biochemical hyperandrogenism, infertility, recurrent miscarriage, insulin resistance, hyperinsulinaemia, gestational diabetes, impaired glucose tolerance, Type 2 diabetes, morbid obesity, hypertension, hypofibrinolysis, hypertriglyceridaemia, low levels of high density lipoprotein-cholesterol and a sevenfold risk increase in cardiovascular disease. Insulin sensitising-lowering agents reduce insulin resistance and hyperinsulinaemia, reverse PCOS endocrinopathy and ameliorate the reproductive, metabolic and cardiovascular morbidity of the disorder. The largest literature on the subject discusses metformin. Improved pregnancy outcomes in women with PCOS receiving metformin may be attributed to its ability to reduce insulin resistance, hyperinsulinaemia and hypofibrinolytic plasminogen activator inhibitor activity by the enhancement of folliculogenesis and improvement of oocyte quality.
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PMID:Treatment of polycystic ovary syndrome with insulin-lowering agents. 1215 Jun 95

Celiac disease is a permanent intolerance to dietary gluten. Its well known features are abdominal symptoms, malabsorption of nutrients, and small-bowel mucosal inflammation with villous atrophy, which recover on a gluten-free diet. Diagnosis is challenging in that patients often suffer from subtle, if any, symptoms. The risk of clinically silent celiac disease is increased in various autoimmune conditions. The endocrinologist, especially, should maintain high suspicion and alertness to celiac disease, which is to be found in 2-5% of patients with insulin-dependent diabetes mellitus or autoimmune thyroid disease. Patients with multiple endocrine disorders, Addison's disease, alopecia, or hypophysitis may also have concomitant celiac disease. Similar heredity and proneness to autoimmune conditions are considered to be explanations for these associations. A gluten-free diet is essential to prevent celiac complications such as anemia, osteoporosis, and infertility. The diet may also be beneficial in the treatment of the underlying endocrinological disease; prolonged gluten exposure may even contribute to the development of autoimmune diseases. The diagnosis of celiac disease requires endoscopic biopsy, but serological screening with antiendomysial and antitissue transglutaminase antibody assays is an easy method for preliminary case finding. Celiac disease will be increasingly detected provided the close association with autoimmune endocrinological diseases is recognized.
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PMID:Endocrinological disorders and celiac disease. 1220 61

The question is whether the administration of estrogenic substances to the human female causes cancer of the endometrium. Current data seems to indicate that in predisposed individuals the unopposed action of estrogenic substances for a considerable period of time will result in endometrial adenomatous hyperplasia, carcinoma in situ (atypical adenomatous hyperplasia), and eventually carcinoma. The relationship of estrogenic substances to the development of endometrial hyperplasia of all degrees is clear, but the relationship of these substances to invasive endometrial cancer is blurred by assumptions based on individual case reports, retrospective reasoning, and uncontrolled experimentation. 4 published reports reviewed here have compared the use of exogenous estrogen by patients with endometrial cancer to that by controls. These studies have not been comprehensive and they raise more questions than they answer. If a physician chooses to use estrogen for the treatment of symptoms or signs of estrogen insufficiency, the selection of patients is crucial. Obesity, hypertension, diabetes, and infertility associated with oligo-ovulation are predisposing factors in the development of endometrial cancer, and patients with these conditions should have endometrial biopsy or uterine aspiration before the institution of therapy. There are 2 therapeutic regimens which can be used to prevent or even reverse the endometrial hyperplasia that may otherwise result from excessive and continuous estrogen administration.
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PMID:Estrogen controversy updated. 1233 9


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