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)

Adipose tissue plays a critical role in energy homeostasis, not only in storing triglycerides, but also responding to nutrient, neural, and hormonal signals and secreting adipokines that control feeding, thermogenesis, immunity, and neuroendocrine function. A rise in leptin signals satiety to the brain through receptors in hypothalamic and brainstem neurons. Leptin activates tyrosine kinase, Janus kinase 2, and signal transducer and activator of transcription 3, leading to increased levels of anorexigenic peptides, e.g., alpha-melanocyte stimulating hormone and cocaine- and amphetamine-regulated transcript, and inhibition of orexigenic peptides, e.g., neuropeptide Y and agouti-related peptide. Obesity is characterized by hyperleptinemia and hypothalamic leptin resistance, partly caused by induction of suppressor of cytokine signaling-3. Leptin falls rapidly during fasting and potently stimulates appetite, reduces thermogenesis, and mediates the inhibition of thyroid and reproductive hormones and activation of the hypothalamic-pituitary-adrenal axis. These actions are integrated by the paraventicular hypothalamic nucleus. Leptin also decreases glucose and stimulates lipolysis through central and peripheral pathways involving AMP-activated protein kinase (AMPK). Adiponectin is secreted exclusively by adipocytes and has been linked to glucose, lipid, and cardiovascular regulation. Obesity, diabetes, and atherosclerosis have been associated with reduced adiponectin levels, whereas adiponectin treatment reverses these abnormalities partly through activation of AMPK in liver and muscle. Administration of adiponectin in the brain recapitulates the peripheral actions to increase fatty acid oxidation and insulin sensitivity and reduce glucose. Although putative adiponectin receptors are widespread in peripheral organs and brain, it is uncertain whether adiponectin acts exclusively through these targets. As with leptin, adiponectin requires the central melanocortin pathway. Furthermore, adiponectin stimulates fatty acid oxidation and reduces glucose and lipids, at least in part, by activating AMPK in muscle and liver.
Obesity (Silver Spring) 2006 Aug
PMID:Adipose tissue as an endocrine organ. 1702 75

Obesity and hypertension are increasing medical problems in adolescents. Serotonin transporter (5-HTT) is involved in mood and eating disturbances. Encoded by the gene SLC6A4, the promoter shows functional insertion/deletion alleles: long (L) and short (S). Because individuals who are carriers for the short version are known to be at risk for higher levels of anxiety, we hypothesized that this variant may be associated with overweight. Data and blood samples were collected from 172 adolescents out of a cross-sectional, population-based study of 934 high school students. To replicate the findings, we also included 119 outpatients from the Nutrition and Diabetes Section of the Children's County Hospital. We found that the S allele was associated with overweight (BMI > 85th percentile), being a risk factor for overweight independently of sex, age, and hypertension [odds ratio (OR): 1.85; 95% confidence interval (CI): 1.13, 3.05; p < 0.02]. Additionally, in the outpatient study, compared with the homozygous LL subjects, S allele carriers showed a higher BMI z-score (1.47 +/- 1.09 vs. 0.51 +/- 1.4; p < 0.002) and were more frequent in overweight children. In conclusion, the S allele of the SLC6A4 promoter variant is associated with overweight being an independent genetic risk factor for obesity.
Obesity (Silver Spring) 2007 Feb
PMID:Short allele of serotonin transporter gene promoter is a risk factor for obesity in adolescents. 1729 98

A 40-year-old male agricultural laborer presented to our clinic with asymptomatic swellings on his left hand and left leg of 2 years' duration. A pea-sized swelling was first noticed on the back of the left hand, which was gradual in onset and slowly progressed to its present size. The patient later noticed multiple swellings over his left leg and thigh, with a similar progression. There was no history suggestive of inflammatory changes or discharge from the lesions. There was no previous history of trauma. The patient was an asthmatic and was on long-term oral steroid therapy (10-20 mg/day prednisolone). None of his family members had similar complaints. On physical examination, the patient was febrile. Cutaneous examination showed multiple, circumscribed, lobulated, non-tender, mobile, cystic swellings of various sizes, ranging from less than 2 cm over the left shin to more than 8 cm over the dorsum of the left hand and ankle (Fig. 1a,b). The surface over these swellings was shiny, smooth, and intact. The skin over the swellings was pliable and normal in color. There was no regional lymphadenopathy. The rest of the clinical examination was normal, except for decreased breath sounds over the left mid and lower pulmonary lobes. Routine laboratory tests, including complete blood count and liver and renal function tests, were within normal limits. Random blood glucose was greater than 400 mg%. Histopathologic examination of one of the cysts (from the hand) showed pheohyphomycotic cysts lined by dense fibrous tissue with chronic inflammatory infiltrate admixed with scattered giant cells in the dermis (Fig. 2). No fungal elements were visualized in the hematoxylin and eosin-stained sections. The fungal elements were found within the cystic cavity on special staining with Gomori's methenamine silver (GMS) and Masson-Fontana stains. The hyphae had irregularly placed branches and showed constrictions around their septae, thus resembling pseudohyphae and yeast forms (Fig. 3). Fine needle aspiration cytology from one of the swellings showed the presence of filamentous fungi on KOH examination and brown-pigmented distorted filaments and yeast-like cells on Masson-Fontana staining (Fig. 4a,b). The positive Masson-Fontana stain was indicative of the presence of melanin in the fungal hyphae, even when the fungal hyphae were not pigmented in the hematoxylin and eosin-stained section. Periodic acid-Schiff reagent also stained the fungal elements, thus confirming our diagnosis of pheohyphomycosis and ruling out the possibility of hyalohyphomycosis. The culture for fungus from the swelling aspirate grew contaminants. The chest X-ray showed dense nodular shadows in the left lower and mid pulmonary lobes. Sputum for acid-fast bacilli and Mantoux test were negative. During the hospital stay, the patient developed high fever and showed altered behavior, for which a computed tomography scan of the brain was performed; this showed evidence of multiple ring enhancing lesions in both frontal lobes. Ultrasound of the abdomen was normal. On the basis of the above findings, a diagnosis of disseminated subcutaneous pheohyphomycosis was made. The patient was given itraconazole, 100 mg twice daily, and his diabetes was managed with insulin. The fever stopped within a week and the altered behavior also started to show an improvement. There was obvious improvement in neurologic signs and symptoms. His skin lesions, however, responded slowly to the treatment. The patient did not report for further follow-up after 1 month.
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PMID:Disseminated pheohyphomycosis. 1734 84

One major pathogenesis in degenerative disorders of the central nervous system (CNS), including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and ischemia, is the oxidative stress induced by reactive oxygen species (ROS). The present study investigated the protective effect of colloidal silver, which is widely marketed as a dietary supplement for diseases like diabetes, AIDS, cancer, and various infections, upon the oxidative brain damage induced by H(2)O(2) or naphthazarin treatment. LDH release from primary cultured astrocytes was enhanced by naphthazarin treatment, and this elevation of the LDH concentration in medium was blocked by colloidal silver treatment. However, hydrogen peroxide was little affected by the colloidal silver. Fluorescence of DCF (peroxides) increased in astrocytes incubated with hydrogen peroxide or naphthazarin compared to the control. When exposed to naphthazarin-induced cells, ROS formation appeared to be reduced by colloidal silver. However, intracellular ROS formation in hydrogen peroxide-treated cells slightly reduced by colloidal silver. These results suggest that colloidal silver has a protective activity against the oxidative stress induced by naphthazarin, but not by hydrogen peroxide.
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PMID:Effect of colloidal silver against the cytotoxicity of hydrogen peroxide and naphthazarin on primary cultured cortical astrocytes. 1736 22

The metabolic syndrome, as defined by the International Diabetes Federation, was investigated in five large, extended, highly consanguineous, healthy Omani Arab families of a total of 1277 individuals. Heritability (h2) of the phenotypic abnormalities that make up the syndrome and other related traits was estimated by variance decomposition method using SOLAR software. The overall prevalence of the syndrome was 23%. The prevalence of abnormalities making the syndrome in a descending order were: obligatory waist circumference, hypertension, raised fasting blood glucose, low serum high-density lipoprotein (HDL), and raised serum triglycerides (TGs). Highly significant, but widely spread, h2 values were obtained for: height (0.68), weight (0.68), BMI (0.68), serum HDL (0.63), serum leptin (0.55), percentage body fat (0.53), total serum cholesterol (0.53), fasting serum insulin (0.51), homeostasis model assessment-insulin resistance index (0.48), serum TG (0.43), waist circumference (0.40), diastolic blood pressure (0.38), and 2-hour glucose level (0.17), whereas for the metabolic syndrome itself, h2 was 0.38. The wide spread of h2 results (0.07 to 0.68) indicates that some determinants, such as weight, BMI, and HDL level, are under significant genetic influence among the Omani Arabs. Other determinants such as insulin resistance, abdominal obesity, diastolic blood pressure, and TG levels seem to be more environmentally driven.
Obesity (Silver Spring) 2007 Mar
PMID:Heritability of determinants of the metabolic syndrome among healthy Arabs of the Oman family study. 1737 3

We examined the genetic association of neuropeptide Y receptor Y5 (NPY5R) single nucleotide polymorphisms (SNPs) with measures of the insulin resistance (metabolic) syndrome. We genotyped 10 NPY5R SNPs in 439 Mexican American individuals (age=43.3+/-17.3 years and BMI=30.0+/-6.7 kg/m2) distributed across 27 pedigrees from the San Antonio Family Diabetes Study and performed association analyses using the measured genotype approach as implemented in Sequential Oligogenic Linkage Analysis Routines (SOLAR). Minor alleles for five (rs11100493, rs12501691, P1, rs11100494, rs12512687) of the NPY5R SNPs were found to be significantly (p<0.05) associated with fasting plasma triglyceride concentrations and decreased high-density lipoprotein concentrations. In addition, the minor allele for SNP P2 was significantly associated (p=0.031) with a decreased homeostasis model assessment of beta-cell function (HOMA-%beta). Linkage disequilibrium between SNP pairs indicated one haplotype block of five SNPs (rs11100493, rs12501691, P1, rs11100494, rs12512687) that were highly correlated (r2>0.98). These preliminary results provide evidence for association of SNPs in the NPY5R gene with dyslipidemia (elevated triglyceride concentrations and reduced high-density lipoprotein levels) in our Mexican American population.
Obesity (Silver Spring) 2007 Apr
PMID:Association of neuropeptide Y receptor Y5 polymorphisms with dyslipidemia in Mexican Americans. 1742 13

We recently showed that long-term weight reduction changes the gene expression profile of adipose tissue in overweight individuals with impaired glucose tolerance (IGT). One of the responding genes was X-chromosomal tenomodulin (TNMD), a putative angiogenesis inhibitor. Our aim was to study the associations of individual single nucleotide polymorphisms and haplotypes with adiposity, glucose metabolism, and the risk of type 2 diabetes (T2D). Seven single nucleotide polymorphisms from two different haploblocks were genotyped from 507 participants of the Finnish Diabetes Prevention Study (DPS). Sex-specific genotype effects were observed. Three markers of haploblock 1 were associated with features of adiposity in women (rs5966709, rs4828037) and men (rs11798018). Markers rs2073163 and rs1155794 from haploblock 2 were associated with 2-hour plasma glucose levels in men during the 3-year follow-up. The same two markers together with rs2073162 associated with the conversion of IGT to T2D in men. The risk of developing T2D was approximately 2-fold in individuals with genotypes associated with higher 2-hour plasma glucose levels; the hazard ratios were 2.192 (p = 0.025) for rs2073162-A, 2.191 (p = 0.027) for rs2073163-C, and 1.998 (p = 0.054) for rs1155974-T. These results suggest that TNMD polymorphisms are associated with adiposity and also with glucose metabolism and conversion from IGT to T2D in men.
Obesity (Silver Spring) 2007 May
PMID:Tenomodulin is associated with obesity and diabetes risk: the Finnish diabetes prevention study. 1749 83

There are at least 6 well-studied imprinting domains on human autosomes. Each domain is under the regulatory control of an 'imprinting centre' that harbours a differentially methylated region. A number of molecular mechanisms result in differential silencing of some genes within these domains and gene expression is tightly regulated in normal individuals. However, this makes them vulnerable to naturally occurring genetic and epigenetic aberrations. Nine recognisable developmental syndromes have been described due to abnormalities within these 6 domains: transient neonatal diabetes (TND; at 6q24); Beckwith- Wiedemann syndrome (BWS) and Silver-Russell syndrome (at 11p15.5; 2 imprinted domains); maternal and paternal uniparental disomy syndromes (at 14q32); Angelman and Prader-Willi syndromes (at 15q11-13), and pseudohypoparathyroidism type 1b (at 20q12-13). Furthermore, it is now recognised that involvement at multiple domains can occur simultaneously and result in what has been described as the hypomethylation syndrome. TND and BWS are discussed in more detail as examples of imprinting disorders.
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PMID:Imprinting in human disease with special reference to transient neonatal diabetes and Beckwith-Wiedemann syndrome. 1792 74

We report the case of a 62-year-old man with a long-standing lesion on the dorsum of his right foot. The patient had diabetes mellitus and was under treatment with oral antidiabetic agents. The lesion contained abundant necrotic tissue, the borders showed evident signs of inflammation, and there was abundant prurulent exudate. Symptoms of infection were observed and a long course of broad-spectum antibiotics was administered. Given the site and characteristics of the lesion, unselective cleansing techniques were avoided. Collagen powder and silver dressing were applied to control bacteria and finally alginate and silicone sponge dressings were applied to soak up the exudate and keep the area moist. After 22 weeks of treatment, evident signs of improvement were observed, allowing the patient to perform activities of daily living.
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PMID:[Treatment of a long-standing lesion with early stimulation of wound healing]. 1803 41

This review aims to provide a rational and ethical basis for prenatal testing for uniparental disomy (UPD) in cases with abnormal ultrasound findings or numeric and/or structural chromosomal aberrations in chorionic villous or amniotic fluid samples. The clinical phenotypes of the genomic imprinting-associated paternal UPD 6 (transient neonatal diabetes mellitus), maternal UPD 7 (Silver-Russell syndrome), paternal UPD 11p (Beckwith-Wiedemann syndrome), maternal UPD 14 (precocious puberty, short stature and highly variable developmental delay), paternal UPD 14 (polyhydramnios and a bell-shaped thorax), maternal UPD 15 (Prader-Willi syndrome), paternal UPD 15 (Angelman syndrome), maternal UPD 16 and UPD 20, as well as the diagnostic options, are summarized. In addition, the clinical impact of UPD testing and its relevance in various prenatal diagnostic situations are discussed. As a general rule, prenatal UPD testing, following genetic counseling, is justified if paternal UPD 14, maternal UPD 15 or paternal UPD 15 are suspected. In contrast, considering the mild phenotypes of paternal UPD 6 and maternal UPD 7, prenatal UPD testing is questionable. Because of the highly variable phenotype for paternal UPD 11p, maternal UPD 14 and maternal UPD 16, prenatal testing should be discussed critically on an individual basis. For all other chromosomes, prenatal UPD testing is purely academic and should therefore not be performed on a routine basis, particularly because a positive result might confuse the parents more than it actually helps them.
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PMID:Prenatal testing for uniparental disomy: indications and clinical relevance. 1805 71


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