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)

Immune cells carry receptors for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; vitamin D receptor (VDR)] and individuals with severe vitamin D deficiency have immune abnormalities. The aim of this study was to investigate the role of vitamin D in the immune system by studying VDR-knockout (VDR-KO) mice. VDR-KO mice had the same metabolic phenotype as rachitic animals with severe hypocalcemia. Leukocytosis, lymphocyte subset composition in different immune organs, and splenocyte proliferation to several stimuli were normal, except for a lower response to anti-CD3 stimulation (simulation index [SI] of 13 +/- 4 vs. 24 +/- 9 in wild-type mice; p < 0.01). Macrophage chemotaxis was impaired (41 +/- 19% vs. 60 +/- 18% in wild-type mice; p < 0.01) but phagocytosis and killing were normal. In vivo rejection of allogeneic (31 +/- 12 days vs. 45 +/- 26 days of survival in wild-type mice, NS) or xenogeneic (10 +/- 2 days vs. 16 +/- 9 days of survival in wild-type mice, NS) islet grafts was comparable with wild-type mice. Surprisingly, VDR-KO mice were protected from low-dose streptozotocin-induced diabetes mellitus (LDSDM; 5% vs. 65% in wild-type mice; p < 0.001). Correcting hypocalcemia by use of lactose-rich or polyunsaturated fat-rich diets fully restored the immune abnormalities in vitro and the sensitivity to diabetes in vivo. On the other hand, treatment with 1,25(OH)2D3 protected wild-type mice against diabetes but did not protect normocalcemic VDR-KO mice. We conclude that immune defects observed in VDR-KO mice are an indirect consequence of VDR disruption because they can be restored by calcium homeostasis normalization. This study proves that although 1,25(OH)2D3 is a pharmacologic and probably a physiological immunomodulator, its immune function is redundant. Moreover, we confirm the essential role of calcium in the immune system.
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PMID:In vitro and in vivo analysis of the immune system of vitamin D receptor knockout mice. 1169 2

Hirschsprung's disease (HD) is considered a focal disease usually confined to the distal colon and rectum. However, autonomic dysfunction and dysmotility in the upper gastrointestinal tract have been reported, suggesting that this disease is not only confined to the distal gastrointestinal tract. This study examines the fasting and postprandial levels of glucose and insulin in adult patients with HD to elucidate whether there might also be an endocrine involvement in this disease. Sixteen patients with surgically treated HD during early childhood and 17 healthy subjects were studied. All subjects ingested a caloric liquid meal containing glucose, lactose, maize oil, and water (2,020 kJ) after an overnight fast. Blood samples were collected at regular intervals for insulin and glucose analyses. Fasting levels of both glucose (P <.05) and insulin (P <.02) were significantly higher in patients compared with healthy controls. Peak concentration of insulin following meal intake was significantly higher in the patient group (P <.05), and peak concentration of glucose tended to be higher in patients compared with controls (P =.06). There was no correlation between body mass index and serum levels of glucose or insulin. The present study shows that adult patients treated for HD during childhood have an impaired glucose and insulin homeostasis, indicating a mild degree of insulin resistance. This may imply susceptibility towards development of non-insulin-dependent diabetes mellitus.
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PMID:Are patients with Hirschsprung's disease prediabetic? 1173 80

We describe a patient with Fanconi-Bickel syndrome diagnosed by clinical manifestations and the identification of a novel mutation in the GLUT 2 gene. She was initially diagnosed with neonatal diabetes mellitus due to hyperglycaemia and glycosuria at 3 days of life. In addition, newborn screening for galactosaemia revealed hypergalactosaemia. Thereafter, she was managed with lactose-free milk and insulin therapy. However, she failed to grow and her liver became progressively enlarged. Her liver function deteriorated with increased prothrombin time. A liver biopsy done at age 9 months showed micronodular cirrhosis with marked fatty changes and she succumbed to hepatic failure with pneumonia at 10 months of age. DNA sequencing analysis of the GLUT 2 gene using her genomic DNA revealed a novel mutation in codon 5, lysine5 stop(K5X).
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PMID:Identification of a novel mutation in the GLUT2 gene in a patient with Fanconi-Bickel syndrome presenting with neonatal diabetes mellitus and galactosaemia. 1202 58

The development of immune-mediated diabetes in BB rats may involve a defect of the gastrointestinal tract (GI), as suggested by increased gut permeability. This study aimed at measuring invertase, maltase, lactase, and peroxidase activities in the duodenum of diabetesprone BioBreeding (BBdp) rats and control BioBreeding rats (BBc) given free access to NIH-07 diet up to the time of killing at 60 66 d of age. After washing the entire small intestine, the duodenal mucosa was scraped off in the first 5-cm segment from the pylorus and frozen in distilled water. Invertase, maltase, and lactase activities were measured by monitoring the conversion of [U-(14)C]sucrose, [U-(14)C]maltose, and [D-[1-(14)C]glucose] lactose to radioactive hexoses, which were phosphorylated in the presence of adenosine triphosphatase and yeast hexokinase and then separated from their precursor by ion-exchange chromatography. Peroxidase activity was measured by a spectrophotometric procedure. In the BBdp rats, the activity of invertase, maltase, and lactase averaged, respectively, 70.2 +/- 4.4, 81.2 +/- 4.3, and 75.7 +/- 4.1% (n = 16 and p < 0.001 in all cases) of the control values found in BBc rats of the same sex. Inversely, after exclusion of two female BBc rats with abnormally high plasma D-glucose concentration, the activity of peroxidase in the BBdp rats averaged 157.4 +/- 20.0% (n = 16; p < 0.02) of the mean control value recorded in BBc rats of the same sex (100.0 +/- 9.3%; n = 14). These findings are compatible with the view that a proinflammatory state of the GI associated with compromise function may precede the occurrence of pancreatic insulitis in BBdp rats and, possibly, human subjects with type 1 diabetes.
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PMID:Invertase, maltase, lactase, and peroxidase activities in duodenum of BB rats. 1262 29

Type 1 diabetes incidence increases at about 3% per year in the Western world. From genetically predisposed people only 20-50% develop the disease. To unravel these mysteries, literature was searched to determine the disease background and to find suggestions for research and prevention. A promising hypothesis was found: the enzyme glutamic acid decarboxylase (GAD) in bacteria may be the source of type 1 diabetes. Epidemiological data can be accounted for this possibility. GAD-containing bacteria can originate from raw foods, especially salted or dried or smoked raw meat and fish products or from proliferation in the ileum of the human small intestine. Proliferation of GAD-containing bacteria in the ileum is probably the most frequent causation of type 1 diabetes. This proliferation is stimulated by the consumption of nitrate-containing ingredients such as vegetables, fruits or nitrate-polluted water and by sugars dissolved in liquids, for example lactose in milk or sugars in juicy fruits and fruit-juices. In the ileum GAD is released from bacteria by endocrine enzymes of the small intestine. Released GAD enters Peyer's patches (PP) in the ileum wall, where it is bound or enclosed by immune cells. These cells move GAD by the lymph- and bloodstream to the immune system for priming and elimination. In case of type 1 diabetes, however, malfunction of PP causes GAD freely move in the lymph stream where it settles on vascular endothelial cells and pancreatic beta-cells. GAD-settlement on beta-cells gives an inflammatory immune response, leading to destruction of the beta-cells and to type 1 diabetes. A perspective for prevention of the disease in predisposed individuals is discussed. It is concluded that GAD-containing bacteria and malfunction of PP should be taken into account in future type 1 diabetes research.
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PMID:Bacteria of food and human intestine are the most possible sources of the gad-trigger of type 1 diabetes. 1592 5

More than 20% of the genes sequenced thus far appear to encode polytopic transmembrane proteins involved in a multitude of critical functions, particularly energy and signal transduction. Many are important with regard to human disease (e.g., depression, diabetes, drug resistance), and many drugs are targeted to membrane transport proteins (e.g., fluoxetine and omeprazole). However, the number of crystal structures of membrane proteins, especially ion-coupled transporters, is very limited. Recently, an inward-facing conformer of the Escherichia coli lactose permease (LacY), a paradigm for the Major Facilitator Superfamily, which contains almost 4000 members, was solved at about 3.5 A in collaboration with Jeff Abramson and So Iwata at Imperial College London. This intensively studied membrane transport protein is composed of two pseudo-symmetrical 6-helix bundles with a large internal cavity containing bound sugar and open to the cytoplasm only. Based on the structure and a large body of biochemical and biophysical evidence, a mechanism is proposed in which the binding site is alternatively accessible to either side of the membrane.
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PMID:Structure and mechanism of the lactose permease. 1595 Jan 62

A new, simple and sensitive pre-column high-performance chromatographic method for the determination of diabetes marker d-glucose, 1,5-anhydro-d-glucitol and related compounds is reported. Sugars (d-glucose, d-galactose, d-mannose, sucrose and arabinose) were derivatized with benzoic acid (BA) at 80 degrees C for 60 min. l-Fucose, fructose, d-lactose, l-rhamnose, arabinose and ascorbic acid were not reacted. Sugar alcohols (xylitol, erythritol, mannitol, sorbitol myo-inositol) were also derivatized with BA at 80 degrees C for 60 min. The fluorescence derivatives were separated on a TSK amide 80 column (4.6 mm i.d. x 250 mm, 5 microm) with acetonitrile-50 mm acetate buffer (pH 5.6; 4:96, v/v) as the mobile phase. The detection wavelength of beizoic acid derivatives was lambda(ex) 275 nm and lambda(em) 315 nm. The detection limits of sugars were 10-80 microg/mL. The calibration graphs were linear up to 10 mg/mL. The relative standard deviations of 500 microg/mL sugars were 7.0-7.3%. The proposed method was compared with the enzymatic photometric glucose analysis method (Glucose B-Test II Wako). The correlation coefficient was 0.83 (n = 20) and y = 0.82x + 5.91, where y and x are concentrations in microg/mL obtained by the proposed pre-column HPLC and enzyme-photometric method, respectively. The detection limits of sugar alcohols were 100-1000 ng/mL. The calibration graphs were linear to 50 microg/mL and relative standard deviations of 10 microg/mL were 7.2-8.2%. The 1,5-AG data by the proposed method was also compared with the enzymatic photometric 1,5-AG analysis method (Rana AG 1,5-AG determination kit, Nihon Kayaku) and good correlation (r = 0.91, n = 20) was also obtained. The proposed method was applied to the simultaneous determination of d-glucose, 1,5-AG and related sugar alcohols in serum from healthy males.
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PMID:Simultaneous determination of glucose, 1,5-anhydro-d-glucitol and related sugar alcohols in serum by high-performance liquid chromatography with benzoic acid derivatization. 1616 Nov 84

The "thrifty genotype hypothesis" has become firmly entrenched as one of the orienting concepts in biomedical anthropology, since first being proposed by Neel (1962 Am. J. Hum. Genet. 14:353-362) over 40 years ago. Its influence on inquiries into the evolutionary origins of diabetes, lactose tolerance, and other metabolic disorders can hardly be underestimated, as evidenced by its continued citation in many top scientific and medical journals. However, its fundamental assumption, that foragers are more likely to experience regular and severe food shortages than sedentary agriculturalists, remains largely untested. The present report tests this assumption by making a cross-cultural statistical comparison of the quantity of available food and the frequency and extent of food shortages among 94 foraging and agricultural societies as reported in the ethnographic record. Our results indicate that there is no statistical difference (P < 0.05) in the quantity of available food, or the frequency or extent of food shortages in these reports between preindustrial foragers, recent foragers, and agriculturalists. The findings presented here add to a growing literature that calls into question assumptions about forager food insecurity and nutritional status in general, and ultimately, the very foundation of the thrifty genotype hypothesis: the presumed food shortages that selected for a "thrifty" metabolism in past foraging populations.
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PMID:Exploring the thrifty genotype's food-shortage assumptions: a cross-cultural comparison of ethnographic accounts of food security among foraging and agricultural societies. 1648 98

A staggering 4000 million people cannot digest lactose, the sugar in milk, properly. All mammals, apart from white Northern Europeans and few tribes in Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into galactose and glucose, after weaning. Lactose intolerance causes gut and a range of systemic symptoms, though the threshold to lactose varies considerably between ethnic groups and individuals within a group. The molecular basis of inherited hypolactasia has yet to be identified, though two polymorphisms in the introns of a helicase upstream from the lactase gene correlate closely with hypolactasia, and thus lactose intolerance. The symptoms of lactose intolerance are caused by gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial toxins may play a key role in several other diseases, such as diabetes, rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose intolerance has been exacerbated because of the addition of products containing lactose to various foods and drinks without being on the label. Lactose intolerance fits exactly the illness that Charles Darwin suffered from for over 40 years, and yet was never diagnosed. Darwin missed something else--the key to our own evolution--the Rubicon some 300 million years ago that produced lactose and lactase in sufficient amounts to be susceptible to natural selection.
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PMID:The molecular basis of lactose intolerance. 1680 12

Commercial milk is homogenized for the purpose of physical stability, thereby reducing fat droplet size and including caseins and some whey proteins at the droplet interface. This seems to result in a better digestibility than untreated milk. Various casein peptides and milk fat globule membrane (MFGM) proteins are reported to present either harmful (e.g. atherogenic) or beneficial bioactivity (e.g. hypotensive, anticarcinogenic and others). Homogenization might enhance either of these effects, but this remains controversial. The effect of homogenization has not been studied regarding the link between early cow's milk consumption and occurrence of type I diabetes in children prone to the disease and no link appears in the general population. Homogenization does not influence milk allergy and intolerance in allergic children and lactose-intolerant or milk-hypersensitive adults. The impact of homogenization, as well as heating and other treatments such as cheesemaking processes, on the health properties of milk and dairy products remains to be fully elucidated.
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PMID:On the supposed influence of milk homogenization on the risk of CVD, diabetes and allergy. 1734 70


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