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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a rare case of sertoliform endometrioid carcinoma of the endometrium in a 71-year-old African American woman who presented with postmenopausal bleeding. Her medical condition was remarkable for hypertension, diabetes, and obesity. She underwent total hysterectomy, right salpingo-oophorectomy and lymph node sampling. The endometrium was occupied by a 4.5-cm solid polypoid tumor, which grossly invaded into the myometrium. Microscopically, the tumor consisted of small hollow tubules, anastomosing cords and trabeculae, and tightly packed nests. Microglandular areas mimicking adult granulosa cell tumors were also present. But true Call-Exner bodies were absent. Component of typical endometrioid carcinoma was noted only focally. The uninvolved endometrium demonstrated atypical complex hyperplasia. The tumor cells were diffusely immunoreactive for epithelial membrane antigen, estrogen receptor, and progesterone receptor (PR), and focally for vimentin. The tumor cells were also diffusely positive for inhibin alpha and CD99. Immunostains for other sex cord markers (calretinin, WT-1, and Melan-A) were also positive in approximately 30% to 40% of the tumor cells. Immunostains for CD10, smooth muscle actin, desmin, or HHF35 were negative. Two ovarian sertoliform endometrioid carcinomas from our archived tissue were, however, immunoreactive for epithelial membrane antigen but negative for inhibin alpha. Despite the prominent sertoliform features, both histologically and immunohistochemically, the tumor was of a high-grade endometrial carcinoma and will likely behave as such. As of today, dual differentiation of epithelium and sex cord by immunohistochemical staining has not been demonstrated in sertoliform endometrioid carcinomas of either endometrial or ovarian origin. Our case is the first documentation of such example and suggests that endometrial carcinoma can undergo true sex cord differentiation.
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PMID:Sertoliform endometrioid carcinoma of the endometrium with dual immunophenotypes for epithelial membrane antigen and inhibin alpha: case report and literature review. 1758 14

Several studies have shown that the adult pancreas possesses a limited potential for beta-cell regeneration upon tissue injury. One of the difficulties in studying beta-cell regeneration has been the lack of a robust, synchronized animal model system that would allow controlled regulation of beta-cell loss and subsequent proliferation in adult pancreas. Here we present a transgenic mouse regeneration model in which the c-Myc transcription factor/mutant estrogen receptor (cMycER(TAM)) fusion protein can be specifically activated in mature beta-cells. We have studied these transgenic mice by immunohistochemical and biochemical methods to assess the ablation and posterior regeneration of beta-cells. Activation of the cMycER(TAM) fusion protein results in synchronous and selective beta-cell apoptosis followed by the onset of acute diabetes. Inactivation of c-Myc leads to gradual regeneration of insulin-expressing cells and reversal of diabetes. Our results demonstrate that the mature pancreas has the ability to fully recover from almost complete ablation of all existing beta-cells. Our results also suggest the regeneration of beta-cells is mediated by replication of beta-cells rather than neogenesis from pancreatic ducts.
Diabetes 2008 Apr
PMID:Regulated beta-cell regeneration in the adult mouse pancreas. 1808 86

There is increasing interest in developing better drugs for improving the health of women. Because of the multiple target organs for estrogens and the occurrence of both beneficial and unwanted effects during treatment, the key to improvement in drug therapy is the development of estrogen receptor modulators with better tissue selectivity. The recent discovery that there are not one but two estrogen receptors, ERalpha and ERbeta, each with its unique tissue distribution and with differing and sometimes opposing actions on certain genes, promises new hope for the development of novel, tissue-selective estrogens. Our present knowledge of the tissue distribution of ERalpha and ERbeta suggests that development of selective therapies for treatment and/or prevention of menopausal symptoms, osteoporosis, cardiovascular disease, type II diabetes, Alzheimer's disease and urinary incontinence is an achievable goal in the foreseeable future. Furthermore, it is possible that future estrogen therapy might be beneficial for men.
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PMID:ERbeta: a novel estrogen receptor offers the potential for new drug development. 1840 12

Hachimi-jio-gan is widely used to improve several disorders associated with diabetes, but its mechanism remains poorly understood. In an attempt to clarify the mechanism of Hachimi-jio-gan, we investigated the effects of this herbal medicine and its components in transfection studies of CV1 cells, especially nuclear receptor-mediated actions. One half (0.5) mg/ml of Hachimi-jio-gan activated peroxisome proliferator-activated receptor (PPARalpha), mediating the activation by 3.1-fold on DR1 response elements; however, it did not affect PPARgamma, thyroid hormone receptor, androgen receptor, estrogen receptor or RXR. In addition, this activation was observed in a dose-dependent manner. Next, to determine which components of Hachimi-jio-gan activate PPARalpha-mediated transcription, 8 of its components (rehmanniae radix, orni fructus, dioscoreae rhizoma, alismatis rhizoma, hoelen, moutan cortex, cinnamomi cortex, aconiti) were tested. Only cinnamomi cortex (1.0 mg/ml) increased PPARalpha-mediated transcription by 4.1-fold, and this activation was specific for PPAR alpha, and not for other nuclear receptors. Moreover, this PPARalpha-related activation by cinnamomi cortex is specifically observed in renal cells. Taken together, these findings indicate that Hachimi-jio-gan and cinnamomi cortex may have a pharmacological effect through the target site for PPARalpha.
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PMID:Herbal medicine, Hachimi-jio-gan, and its component cinnamomi cortex activate the peroxisome proliferator-activated receptor alpha in renal cells. 1846 82

Estrogen is known to affect vascular function and diabetes development, but the relative contribution of estrogen receptor (ER) isoforms is unclear. The aim of this study was to determine how individual ER isoforms modulate inflammatory enzymes in the vascular wall of control and streptozotocin (STZ)-injected rodents. Primary cultures of rat aortic smooth muscle cells (SMCs) were stimulated with inflammatory agents in the presence or absence of increasing concentrations of the ER alpha and ER beta-selective agonists 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) and diarylpropionitrile (DPN), respectively. The production of inducible nitric-oxide synthase (iNOS), a classical indicator of vascular inflammation, was significantly reduced by PPT in control but not diabetic SMCs, whereas it was further enhanced by DPN treatment in both groups. This distinct action profile was not related to changes in ER transcriptional activity. However, extracellular signal-regulated kinase 1/2 signaling was activated by DPN but not by PPT in cytokine-treated SMCs. In cultured aortic rings from both normoglycemic and STZ-diabetic mice, pharmacological activation of ER alpha attenuated cytokine-driven iNOS induction by 30 to 50%. Vascular iNOS levels were decreased consistently when adding 1 nM 17beta-estradiol to aortic tissues from ER beta- but not ER alpha-knockout mice. These findings suggest a possible role for ER alpha-selective ligands in reducing vascular inflammatory responses under normo- and hyperglycemic conditions.
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PMID:Distinct roles of estrogen receptor-alpha and beta in the modulation of vascular inducible nitric-oxide synthase in diabetes. 1883 49

The purpose of the treatment of osteoporosis is to reduce fracture risk and maintain/improve quality of life (QOL). The criteria for initiating pharmacotherapy to prevent fragility fractures should be provided separately from the criteria for diagnosis of osteoporosis. In Japan, low bone mineral density (BMD), prevalent fracture, and age are established as fracture risk factors from available data. A meta-analysis conducted by the WHO assured that excessive drinking (2 units a day or more), current smoking, and a family history of hip fracture are fracture risk factors. Moreover, in WHO technical report 921, high levels of CTX, a bone resorption marker as well as uncarboxylated osteocalcin were cited as risk factors of hip fracture, which can be measured in medical practice in Japan. Pharmacotherapy should be initiated with the consideration of the above risk factors. Recent large scale of randomized control trial(RCT), followed by meta-analysis demonstrated that bisphosphonates such as alendronate and risedronate as well as raloxifene (selective estrogen receptor modulator) are top grade of drugs which prevent fragility fracture in osteoporotic patients. Now, it is possible to perform evidence-based medicine in daily medical practice. As for secondary osteoporosis, along with treatment of underlying diseases, treatment aimed at preventing bone loss is necessary in many cases. Accumulating evidence is available about increased fracture threshold in glucocorticoid- and diabetes mellitus-induced osteoporosis. Therefore, early treatment should be appropriate in these cases. In osteoporotic patients, atherosclerotic vascular calcification as well as abnormal lipid metabolism often coexists. Multiple vertebral fractures followed by kyphosis often causes functional disorders of the digestive and respiratory systems.
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PMID:[Progress in the treatment of osteoporosis]. 1906 85

The estrogen receptor ERalpha is emerging as a key molecule involved in glucose and lipid metabolism. The main functions of pancreatic beta-cells are the biosynthesis and release of insulin, the only hormone that can directly decrease blood glucose levels. Estrogen receptors ERalpha and ERbeta exist in beta-cells. The role of ERbeta is still unknown, yet ERalpha plays an important role in the regulation of insulin biosynthesis, insulin secretion and beta-cell survival. Activation of ERalpha by 17beta-estradiol (E2) and the environmental estrogen bisphenol-A (BPA) promotes an increase of insulin biosynthesis through a non-classical estrogen-activated pathway that involves phosphorylation of ERK1/2. The activation of ERalpha by physiological concentrations of E2 may play an important role in the adaptation of the endocrine pancreas to pregnancy. However, if ERalpha is over stimulated by an excess of E2 or the action of an environmental estrogen such as BPA, it will produce an excessive insulin signaling. This may provoke insulin resistance in the liver and muscle, as well as beta-cell exhaustion and therefore, it may contribute to the development of type II diabetes.
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PMID:The pancreatic beta-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes. 1943 49

A decrease in bone mineral density has been reported to be associated with increased progression of aortic stenosis (AS). We hypothesized that osteoporosis treatment (OT) is associated with decreased progression of AS. We performed an observational study of patients with AS from our echocardiographic database comparing 18 patients on OT (bisphosphonates, calcitonin, or estrogen receptor modulators) with 37 patients not on OT. All patients had serial echocardiograms. Patients with mitral stenosis, aortic valve replacement, renal failure, calcium disorders, or left ventricular ejection fraction <40% were excluded. Aortic valve area (AVA) was calculated using the continuity equation. There was no significant difference in age, gender, renal function, hypertension, statin use, diabetes, or calcium level between the 2 groups. Mean baseline AVA was 1.33 cm(2) and not significantly different between groups. After a mean of 2.4 +/- 1.0 years, mean annual changes in AVA were -0.22 +/- 0.22 cm(2) in those not on OT and -0.10 +/- 0.18 cm(2) in patients receiving OT (p = 0.025). There was a graded association between AS progression rate and OT. In a multivariable analysis including age, gender, and statin use, only OT was associated with a change in AVA. In conclusion, OT is strongly and independently associated with decreased progression of AS. This association warrants investigation in a larger, prospective study.
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PMID:Osteoporosis treatment and progression of aortic stenosis. 1957 32

Translational research is a burgeoning science that shows potential to improve the transition of research from bench to bedside. This novel science explores all major aspects of preclinical and clinical issues which are relevant for the success of translational pharmaceutical or medical device/diagnostic innovations. This includes target risk assessment, biomarker evaluation and predictivity grading both for efficacy and toxicity, early human trial design adequate to guide stop/go decisions on grounds of biomarker panels, and biostatistical methods to analyze multiple readout situations and quantify risk projections. Representing a comparably novel science, rapid steroid actions have been recognized to carry potential clinical implications in various fields. Findings in this field have not yet been successfully translated into clinically relevant new medicines except for neurosteroids. A promising compound is the membrane estrogen receptor agonist STX, which may be applicable for estrogen withdrawal symptoms. Nongenomic vitamin D analogs may be useful as antiinflammatory, anticancer or diabetes preventing agents. Further the membrane thyroid receptor agonist tetrac may be useful in cancer treatment. Unfortunately lazaroids (membrane-only active glucocorticoids), which have been clinically tested as neuroprotective agents, had to be abandoned because of lacking clinical efficacy. Yet, the hierarchy of antirheumatic glucocorticoid action in regard to their clinical potency may better correlate with their membrane effects than their ability to bind to the classic glucocorticoid receptor. To improve the translational success of the rapid actions of steroids research, scientists should become familiar with major aspects of translational work and always seek for translational dimensions in their research.
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PMID:Translational research on rapid steroid actions. 1978 96

The prevalence of diabetes is lower in premenopausal women, especially diabetic syndromes with insulin deficiency, suggesting that the female hormone 17beta-estradiol protects pancreatic beta-cell function. In classical rodent models of beta-cell failure, 17beta-estradiol at physiological concentrations protects pancreatic beta-cells against lipotoxicity, oxidative stress, and apoptosis. In this review, we integrate evidence showing that estrogens and their receptors have direct effects on islet biology. The estrogen receptor (ER)-alpha, ER beta, and the G-protein coupled ER are present in beta-cells and enhance islet survival. They also improve islet lipid homeostasis and insulin biosynthesis. We also discuss evidence that ERs modulate insulin sensitivity and energy homeostasis, which indirectly alter beta-cell biology in diabetic and obese conditions.
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PMID:Minireview: Estrogenic protection of beta-cell failure in metabolic diseases. 1996 78


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