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)

Pheochromocytomas are rare catecholamine-secreting, chromaffin tumors of the autonomic nervous system. Most pheochromocytomas are sporadic, but up to 24% of pheochromocytomas are part of a familial disorder. Here we describe a female patient, who presented to our outpatient clinic 18 years after removal of a pheochromocytoma of the left adrenal gland in China. Now she reported flank pain on the left side and elevated blood pressure. 24-hour urinary catecholamines, metanephrines, and normetanephrines as well as plasma-norepinephrine were elevated. The transabdominal ultrasonography revealed a tumor with reduced echogenicity in the left suprarenal region, which was suspected to be a recurrent pheochromocytoma. This finding was confirmed by MRT and J (123)-MIBG-scan. Parathyroid hormone (PTH) and calcitonin were in the normal range. After surgical excision, histological examination of the adrenal mass proved to be a pheochromocytoma. Molecular genetic analysis with sequencing of the succinate dehydrogenase type B (SDHB) gene revealed a formerly unknown mutation of codon 214 (CAG-->TAG) leading to an amino acid change of glutamine to a stop-Codon (Q214X-mutation) in exon 6. This case report highlights the necessity of re-evaluating patients with nonsyndromic pheochromocytoma who are diagnosed without genetic testing to estimate the risk of a relapse and to initiate testing of first-degree relatives.
Exp Clin Endocrinol Diabetes 2007 Oct
PMID:Relapsing pheochromocytoma in a Chinese women caused by a novel mutation in exon 6 of the SDHB gene: a case report. 1794 98

Flaxseed lignan secoisolariciresinol diglucoside (SDG) has been reported to prevent and alleviate lifestyle-related diseases including diabetes and hypercholesterolaemic atherosclerosis. This study assesses the effect of SDG on the development of diet-induced obesity in mice and the effect of the SDG metabolite enterodiol (END) on adipogenesis in 3T3-L1 adipocytes. We compared body weight, visceral fat weight, liver fat content, serum parameters, mRNA levels of lipid metabolism-related enzymes and adiponectin in mice fed either a low-fat diet (5 % TAG), high-fat diet (30 % TAG) or high-fat diet containing 0.5 and 1.0 % (w/w) SDG for 4 weeks. Administration of SDG to mice significantly reduced high-fat diet-induced visceral and liver fat accumulation, hyperlipaemia, hypercholesterolaemia, hyperinsulinaemia and hyperleptinaemia. SDG also suppressed sterol regulatory element binding protein 1c mRNA level in the liver and induced increases in the adiponectin mRNA level in the white adipose tissue and carnitine palmitoyltransferase I mRNA level in the skeletal muscle. Differentiated 3T3-L1 adipocytes were treated with 0, 5, 10 and 20 mumol/l END and then assayed for mRNA expression of adipogenesis-related genes and DNA binding activity of PPARgamma to the PPAR response element consensus sequence. END induced adipogenesis-related gene mRNA expression including adiponectin, leptin, glucose transporter 4 and PPARgamma, and induced PPARgamma DNA binding activity in 3T3-L1 adipocytes. In conclusion, SDG induced adiponectin mRNA expression and showed beneficial effects on lipid metabolism in diet-induced obesity in mice. Flaxseed lignans are suggested to regulate adipogenesis-related gene expressions through an increase in PPARgamma DNA binding activity.
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PMID:Flaxseed lignan attenuates high-fat diet-induced fat accumulation and induces adiponectin expression in mice. 1825 24

Aqueous extracts or juice from unripened fruit of Momordica charantia (bitter melon) has traditionally been used in the treatment of diabetes and its complications. Insulin resistance is characterized by significant down-regulation of hepatic insulin signalling as documented by attenuated phosphorylation of insulin receptor (IR), IR substrates 1 and 2, phosphoinositide-3 kinase, protein kinase B, and over-expression of phosphotyrosine phosphatase 1B. We recently demonstrated that bitter melon juice (BMJ) is a potent inhibitor of apoB secretion and TAG synthesis and secretion in human hepatoma cells, HepG2, that may be involved in plasma lipid- and VLDL-lowering effects observed in animal studies. The aim of this study was to evaluate the effects of BMJ on plasma apoB levels and hepatic insulin signalling cascade in mice fed high-fat diet (HFD). Female C57BL/6 mice (4-6 weeks old) were randomized into three groups receiving regular rodent chow, HFD and HFD+BMJ. The data indicate that BMJ not only improves glucose and insulin tolerance but also lowers plasma apoB-100 and apoB-48 in HFD-fed mice as well as modulates the phosphorylation status of IR and its downstream signalling molecules. Investigating the biochemical and molecular mechanisms involved in amelioration of diabetic dyslipidaemia by BMJ may lead to identification of new molecular targets for dietary/alternative therapies.
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PMID:Momordica charantia (bitter melon) reduces plasma apolipoprotein B-100 and increases hepatic insulin receptor substrate and phosphoinositide-3 kinase interactions. 1832 95

The role of flavonoids in CVD, especially in strokes, is unclear. Our aim was to study the role of flavonoids in CVD. We studied the association between the intakes of five subclasses (flavonols, flavones, flavanones, flavan-3-ols and anthocyanidins), a total of twenty-six flavonoids, on the risk of ischaemic stroke and CVD mortality. The study population consisted of 1950 eastern Finnish men aged 42-60 years free of prior CHD or stroke as part of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up time of 15.2 years, 102 ischaemic strokes and 153 CVD deaths occurred. In the Cox proportional hazards model adjusted for age and examination years, BMI,systolic blood pressure, hypertension medication, serum HDL- and LDL-cholesterol, serum TAG, maximal oxygen uptake, smoking, family history of CVD, diabetes, alcohol intake, energy-adjusted intake of folate, vitamin E, total fat and saturated fat intake (percentage of energy), men in the highest quartile of flavonol and flavan-3-ol intakes had a relative risk of 0.55 (95% CI 0.31, 0.99) and 0.59 (95% CI 0.30, 1.14) for ischaemic stroke, respectively, as compared with the lowest quartile. After multivariate adjustment, the relative risk for CVD death in the highest quartile of flavanone and flavone intakes were 0.54 (95% CI 0.32, 0.92) and 0.65 (95% CI 0.40, 1.05), respectively. The present results suggest that high intakes of flavonoids may be associated with decreased risk of ischaemic stroke and possibly with reduced CVD mortality.
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PMID:Flavonoid intake and the risk of ischaemic stroke and CVD mortality in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study. 1839 14

We evaluated the role of oxidative stress in diabetic nephropathy by measuring intracellular reactive oxygen species (ROS) and redox-sensitive transcription factors in isolated peripheral mononuclear cells (PBMC) in 66 diabetic patients with or without diabetic nephropathy (Groups III and II, respectively) and 49 normal controls (Group I). Stimulated ROS was significantly higher in Group III compared to Group II (increment of H(2)O(2)-induced ROS production: 21.8+/-2.2% vs. 11.1+/-2.0%; increment of PMA-induced ROS production 23.5+/-4.5% vs. 21.6+/-2.2%; both respectively), and the activity of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1), but not specificity protein 1 (Sp1) was significantly higher in Group III than in Group II (2.53-fold vs. 2.0-fold vs. 1.43-fold, respectively). Both PBMC- and urinary TGF-beta1 levels were higher in Group III than Group II (3.23+/-0.39 ng/g vs. 1.99+/-0.68 ng/g in PBMCs, 16.88+/-6.84 (ng/g Cr) vs. 5.61+/-1.57 (ng/g Cr) in urine, both respectively), and they correlated with the activity of NF-kappaB and AP-1 and 24-h urine albumin excretion (UAE). Increased intracellular ROS generation in PBMCs of diabetic patients is involved in the pathogenesis of diabetic nephropathy via activation NF-kappaB and AP-1 and an increased expression of TGF-beta1.
Diabetes Res Clin Pract 2008 Jul
PMID:The activation of NF-kappaB and AP-1 in peripheral blood mononuclear cells isolated from patients with diabetic nephropathy. 1848 15

The purpose of the present study was to investigate the effects of garlic (Allium sativum L.) on the diabetic nephropathy and oxidative stress induced by STZ (streptozotocin) in rats. Diabetes was induced in Male Sprague-Dawley rats by administering a single intraperitoneal injection of STZ (60 mg/kg of body weight). Administration of garlic, prepared as FGH (fresh garlic homogenate) significantly attenuated STZ-induced diabetic nephropathy as evaluated by assessment of serum glucose, insulin, total TAG (triacylglycerol), TC (total cholesterol) and Ccr (creatinine clearance) in control and STZ-induced diabetic rats. Urinary excretions of albumin and NAG (N-acetyl-beta-D-glucosaminidase) were also reduced following the treatment with FGH. In addition, significant inhibition of TBARSs (thiobarbituric acid-reacting substances) with a marked improvement of GSH content in the kidney homogenates was also observed. Moreover, renal tissue content and urinary excretion of nitrites were markedly decreased in this model, and virtually enhanced to the same levels as in the non-diabetic kidney following FGH supplementation. These data revealed that FGH has the ability to ameliorate STZ-induced diabetic nephropathy possibly through participation in the inhibition of oxidative damage to kidney and/or increased kidney nitric oxide bioavailability.
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PMID:Renal oxidative stress and nitric oxide production in streptozotocin-induced diabetic nephropathy in rats: the possible modulatory effects of garlic (Allium sativum L.). 1858 10

The serum levels of resistin, a 12-kDa protein primarily expressed in inflammatory cells in humans, are increased in patients with chronic kidney disease and in those with diabetes mellitus. Both groups of patients have an increased risk of infections mainly as a result of disturbed polymorphonuclear leukocyte (PMNL) functions. Therefore, we investigated the influence of resistin on human PMNLs. Serum resistin concentrations were determined with a sandwich enzyme immunoassay. Using PMNLs from healthy subjects, chemotaxis was tested by the under-agarose method. Flow cytometric assays to measure oxidative burst and phagocytosis were conducted in whole blood. The uptake of deoxyglucose was determined as measure of the PMNL activation state. The activity of intracellular kinases was assessed by Western blotting and by in vitro kinase assays. Resistin inhibited PMNL chemotaxis and decreased the oxidative burst stimulated by Escherichia coli and by PMA, but did not influence PMNL phagocytosis of opsonized E. coli and PMNL glucose uptake. The inhibition of PMNLs by resistin was observed at concentrations found in serum samples of uremic patients, but not in concentrations measured in healthy subjects. Experiments with specific signal transduction inhibitors and measurements of intracellular kinases suggest that PI3K is a major target of resistin. In conclusion, resistin interferes with the chemotactic movement and the stimulation of the oxidative burst of PMNL, and therefore may contribute to the disturbed immune response in patients with increased resistin serum levels such as uremic and diabetic subjects.
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PMID:Resistin inhibits essential functions of polymorphonuclear leukocytes. 1876 28

Recently, various sets of protein biomarkers have been discovered in important diseases such as cancers, brain stroke, heart attack, diabetes, and so on. Many of these biomarkers are expected to be extremely valuable as targets for clinical diagnosis and drug development; however, the clinical validation is difficult and time-consuming by individual assays or due to very low concentration in an early stage of disease. For the super-sensitive and multiplex detection of target biomarkers, we have developed MUSTag (Multiple Simultaneous Tag) assay technology with innovative modification of the immuno-PCR method. In MUSTag technology, specific antibodies against several important biomarkers were linked to 100-300bp long oligonucleotides as detection tags. Each different oligo-tag simultaneously detects multiplex protein targets with extremely high sensitivity(more than 10 fg (10(-15) g)/ml) in a dose-dependent manner by qRT-PCR-based (maximum 3 plexes) or capillary electrophoretic amplification (over 30 plexes). Here we report our recent results of multiple cytokine assay or disease-specific biomarker assay using MUSTag technology, and further, clinical results from patients with cancers, ischemic brain or heart attack, who need prompt and predictive diagnosis for adequate treatment.
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PMID:[Clinical application of supersensitive and multiplex assay, MUSTag technology]. 1897 59

Hepatocyte nuclear factor (HNF)-1alpha is a homeodomain-containing transcription factor. Humans heterozygous for mutations in the HNF-1alpha gene develop maturity-onset diabetes of the young (MODY3), which is associated with reduced insulin secretion. The mechanisms responsible for defective glucose-induced insulin secretion due to HNF-1alpha deficiency are complex. In order to explore the relationship between HNF-1alpha and beta-cell proliferation, we have created a novel animal model. Mice lacking one allele of the HNF-1alpha gene were crossed with transgenic mice expressing the large T antigen driven by the rat insulin II promoter (RIP). The resulting mouse strains allowed us to study the effect of HNF-1alpha deficiency on the extensive beta-cell proliferation that occurs in these mice. Our results indicate that deficiency of HNF-1alpha severely constrains the extent of beta-cell proliferation occurring in RIP-Tag mice leading to significant changes in blood glucose concentrations as a result of reduced beta-cell number, insulin content, insulin secretion and intracellular responses in Ca(2+). Furthermore expression profiling studies using immortalized cell lines generated from HNF-1alpha/RIP-Tag mice showed changes in expression of genes involved in cellular growth and proliferation. These results provide insights into the mechanisms whereby HNF-1alpha affects beta-cell function.
Diabetes Res Clin Pract 2009 Apr
PMID:Role of HNF-1alpha in regulating the expression of genes involved in cellular growth and proliferation in pancreatic beta-cells. 1918 15

Beneficial effects of n-3 fatty acids on a variety of physiological functions have been reported, but information related to the effects of oily fish consumed within a varied diet on glucose metabolism and diabetes risk is scarce. The objective of the study was to compare the effects of a diet rich in oily fish to those of a diet rich in red meat on lipid profile, oxidative status, glucose metabolism and insulin sensitivity in young, iron-deficient women. The study was designed attending the CONSORT statement guidelines. It was a randomised crossover dietary intervention study with two 8-week periods. Two diets were designed differing only in their oily fish or red meat content (four portions per week). Twenty-five young iron-deficient women with normal lipid, glucose and insulin levels participated in the assay. Lipid profile (total, LDL- and HDL-cholesterol, TAG), fasting glucose, fasting insulin, and oxidation (lipoperoxides) and inflammation (soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1) biomarkers were analysed. Insulin sensitivity was assessed by the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI). Insulin levels significantly decreased and insulin sensitivity significantly increased with the oily fish diet. HDL-cholesterol significantly increased with the oily fish diet. Other parameters did not significantly differ between diets. An increase in oily fish consumption increases insulin sensitivity in young iron-deficient women. This outcome should be considered when giving dietary advice to this population.
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PMID:An oily fish diet increases insulin sensitivity compared to a red meat diet in young iron-deficient women. 1921 Aug 57


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