Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The responsiveness of renin-angiotensin and kallikrein-kinin systems to furosemide challenge has been investigated in forty-six diabetic patients (34 NIDDM/12 IDDM), subdivided into Group I (uncomplicated DM), Group II (DM with hypertension), Group III (DM with nephropathy), Group IV (DM with hypertension and nephropathy) and a control group of 10 healthy volunteers. Plasma renin activity (PRA) was estimated by radioimmunoassay in blood samples drawn before and 10 min after furosemide administration (0.5 mg/kg i.v.). Urinary kallikrein levels were measured by bioassay using estrogenized rat uterus preparation in 4h urine samples collected before and after the diuretic. Urinary Na+ and K+ were also measured. The basal PRA in diabetics was not significantly different from controls, whereas, urinary kallikrein levels were markedly low in all patients. Both PRA and kallikrein levels increased after furosemide in controls while in diabetics this response was severely blunted. In a subset of Group I, a paradoxical fall in PRA and kallikrein levels was noted after furosemide, an effect similar to that observed in patients with nephropathy (Group III). This response in absence of clinical and biochemical parameters of nephropathy indicates early derangement of renal hemodynamic mechanisms heralding the onset of nephropathy.
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PMID:Plasma renin activity and urinary kallikrein excretion in response to intravenous furosemide in diabetic patients. 208 34

Drosophila Crumbs (Crb), Stardust (Sdt), Discs large (Dlg), Scribble (Scrib) and Lethal giant larvae (Lgl) are involved in the establishment and the maintenance of apicobasal polarity in epithelial tissues. Because epithelial polarity is disrupted in tumors, human homologs of Drosophila crb, sdt, dlg, scrib, and lgl are potential cancer-associated genes. MPP1/EMP55, MPP2, MPP3, MPP4, MPP5/PALS1 and MPP6/PALS2 genes are human homologs of Drosoplila sdt. Here, we identified and characterized a novel member of MPP gene family, MPP7, by using bioinformatics. Uncharacterized FLJ32798 cDNAs (BC038105 and AK057360) were derived from human MPP7 gene. BC038105 was a representative MPP7 cDNA, while AK057360 was an aberrant MPP7 cDNA with a frame shift. Human MPP7 mRNA was expressed in placenta, brain, testis as well as in uterus tumor, bladder tumor, and lymphoma. Microsatellite marker D10S588, linked to IDDM and hereditary thrombocytopenia, was located within the MPP7 gene at human chromosome 10p12.1. Nucleotide sequence of mouse Mpp7 cDNA was determined in silico by assembling 3'-truncated cDNA AK078849, genome clone RP24-255J24, and EST AV260217. Human MPP7 showed 92.9% total-amino-acid identity with mouse Mpp7, and 75.7% total-amino-acid identity with zebrafish humpback. MPP7 orthologs were MAGUK proteins with two L27 domains, PDZ domain, SH3 domain, and GuKc domain. MPP7 was most related to MPP3 among MPP family members, functioning as adopter molecules assembling Crb homologs (CRB1, CRB3), Dlt homologs (INADL/PATJ, MPDZ/MUPP1), and Lin-7 homologs (LIN7A, LIN7B, LIN7C). This is the first report on identification and characterization of human MPP7 and mouse Mpp7 genes.
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PMID:Identification and characterization of human MPP7 gene and mouse Mpp7 gene in silico. 1471 43

Insulin-dependent diabetes mellitus is a well-known teratogen, which might cause growth retardation, malformations and fetal death. We have previously shown, that potentiation of the maternal immune system (immunopotentiation) might protect the embryo from diabetes teratogenicity. Therefore, in the present study we further inquired whether diabetes teratogenicity might be associated with alterations in the level of immune effector cells in systemic and local lymphoid organs as well as in the uterus throughout pregnancy and whether the protection exerted by maternal immunopotentiation might be realized through its effect on those cells. Streptozotocin-induced diabetes in ICR mice was found to reduce pregnancy rate and fetal weight while increasing the resorption rate and the percentage of litters with malformed fetuses. These teratogenic effects were accompanied by a decreased percentage of cells expressing Mac-1, Thy-1.2, CD4 or CD8 in the spleen and inguinal as well as paraaortic lymph nodes, except for Mac-1 expression by splenocytes, which increased significantly in the beginning of pregnancy and decreased later. A different pattern was observed in the uterus, when the percentage of cells expressing these markers tended to increase in the beginning of pregnancy and decrease later. Intrauterine immunopotentiation with rat splenocytes was found to improve the reproductive performance of diabetic animals. This protective effect was accompanied by a general normalization of the level of the various cell surface markers, when in most cases their expression returned to that found in nonimmunopotentiated mice. Our results suggest that the protection exerted by maternal immunopotentiation on the embryo against diabetes teratogenicity might be mediated via its effect on the level of immune effector cells localized to uterus and lymphoid organs, which was found to be altered in diabetic mice.
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PMID:Diabetes teratogenicity is accompanied by alterations in macrophages and T cell subpopulations in the uterus and lymphoid organs. 1531 30

Type 1 diabetes, a multifactorial disease involving genetic and environmental factors, results from the destruction of pancreatic beta-cells. The maternal environment has been suggested to be important in the development of diabetes. To assess the role of maternal factors in the development of insulitis and overt diabetes, we transplanted pre-implantation stage embryos of nonobese diabetic (NOD) mice, a model of type 1 diabetes, into the uterus of each recipient. Recipients were ICR and DBA/2J mice without diabetic genetic predisposition and NOD mice not exhibiting overt diabetes during the experiment; offspring were designated as NOD/ICR, NOD/DBA, and NOD/NOD, respectively; unmanipulated NOD offspring were also examined. NOD/ICR and NOD/DBA offspring developed insulitis significantly earlier than NOD/NOD offspring. However, overt diabetes was significantly suppressed in NOD/ICR and NOD/DBA offspring in comparison with NOD/NOD offspring. Insulin autoantibodies (IAAs) were undetectable in ICR and DBA/2J surrogate mothers and in NOD/ICR and NOD/DBA offspring at the onset of insulitis, suggesting that maternal factors other than transmitted IAAs induced the earlier onset. The present study indicates that altered maternal factors modify the immune response to islets, which in turn might affect the pathogenic course from insulitis to overt diabetes.
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PMID:Maternal factors in a model of type 1 diabetes differentially affect the development of insulitis and overt diabetes in offspring. 1598 3

Type 1 diabetes results from the destruction of pancreatic b-cells (insulitis). It is a multifactorial disease involving genetic and environmental factors, including the maternal environment. Viruses have also been implicated in the pathogenesis of human type 1 diabetes as well as in its model non-obese diabetic (NOD) mice during the perinatal period, as endogenous viruses and/or as infectious agents vertically transmitted from mothers. However, the role of virus as genetic or environmental factor and its interaction with other maternal factors remain unclear. In a series of experiments, we transplanted preimplantation-stage NOD embryos into the uterus of recipient Institute of Cancer Research (ICR) mice, which are without diabetic genetic predisposition, and NOD mice, which did not exhibit overt diabetes during the experiment, and designated offspring as NOD/ICR and NOD/NOD, respectively. We previously observed that NOD/ICR offspring developed insulitis significantly earlier than NOD/NOD offspring. To assess the role of viruses in the development of insulitis, we examined the appearance of viral particles and expression of retroviruses between NOD/ICR and NOD/NOD. NOD/ICR showed earlier expression of env region of the xenotropic type C retrovirus by polymerase chain reaction analysis than NOD/NOD, while the retrovirus-like particles were observed in the islet b-cells similarly in both groups by electron microscopy. Serum corticosterone level, which is suggested to enhance retroviral induction, was significantly higher in the ICR than in the NOD surrogate mothers. These findings suggest that the observed virus is endogenous and that maternal environmental factors, including hormone levels, affect the induction of endogenous viruses and cause the earlier onset of insulitis.
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PMID:Maternal environment affects endogenous virus induction in the offspring of type 1 diabetes model non-obese diabetic mice. 1613 64

Neoplasia was established in 5.4% out of 15,813 patients with diabetes mellitus registered at the City Population-Based Cancer Register and Territorial Diabetic Center, St. Petersburg. Gender-unrelated decreasing order of tumor sites was as follows: breast, skin, uterus, colon and stomach. Broncho-pulmonary and gastric cancer incidence in male patients with diabetes was higher than in females (3.5 and 2.2 times, respectively). The relationship was reversed with thyroid cancer and skin melanoma (4.4 and 2.3 times, respectively). In patients with type 1 diabetes mellitus (10.3%), the cancer incidence pattern differed significantly from that in the whole diabetes-associated cohort of cancer patients: the former tended to involve such sites as pancreas, urinary bladder, stomach, cervix uteri, lung and skin. Data on age at diagnosis of cancer or diabetes, insulin therapy intensity and body mass were evaluated. The value of timely screening for both cancer and diabetes mellitus in such cohorts was confirmed.
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PMID:[Registry-based analysis of cancer and diabetes combination: prevalence and features]. 1819 8

Effects of isoflavones on estrogen sensitive tissues are discussed controversially. This study was designed to investigate tissue specific effects of an isoflavone exposure through different periods of life in female Wistar rats and to compare the effects of genistein (GEN) to those of mixed dietary isoflavones, GEN and daidzein (DAI). One group received an isoflavone-free diet (IDD), another was fed an isoflavone-rich diet (IRD) and the third group an IDD supplemented with GEN (GEN(d)) prior to mating, throughout pregnancy and up to weaning. The offspring were kept on the respective diets during growth, puberty and adulthood. The weight of the uterus, the height of the uterine and vaginal epithelium, the bone mineral density of the tibia, and the expression of the estrogen sensitive gene CaBP9K in the liver were determined. At d21, the uterine weight, the uterine epithelium and the expression of CaBP9K in the liver were significantly stimulated in GEN(d) animals compared to IDD and IRD. Interestingly, bone mineral density was increased in GEN(d) and in IRD animals. Around puberty (d50) neither uterine wet weights nor trabecular bone density differed significantly among the isoflavone groups and the IDD control. At d80 no significant differences in uterine weight were observed among IDD, GEN(d) and IRD animals. However, bone mineral density was increased in GEN(d) and IRD animals. In summary, our results demonstrate that lifelong dietary exposure to isoflavones can affect estrogen sensitive tissues, apparently in a tissue selective manner. With respect to health risk and benefit our data indicate that an increased bone mineral density can be achieved by lifelong exposure to an IRD, which, in contrast to GEN supplementation, does not seem to stimulate the proliferation of the uterine epithelium.
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PMID:Responses of estrogen sensitive tissues in female Wistar rats to pre- and postnatal isoflavone exposure. 1973 40

Emerging biotechnologies, such as the use of biohybrid devices for cellular therapies, are showing increasing therapeutic promise for the treatment of various diseases, including type 1 diabetes mellitus. The functionality of such devices could be greatly enhanced if successful localized immunosuppression regimens could be established, since they would eliminate the many otherwise unavoidable side effects of currently used systemic immunosuppressive therapies. The existence of local immune privilege at some specialized tissues, such as the eye, CNS, or pregnant uterus, supports the feasibility of localized immunomodulation, and such an approach is particularly well-suited for cell transplant therapies where all transplanted tissue is localized within a device. Following the success of syngeneic transplantation in a subcutaneous prevascularized device as a bioartificial pancreas in a rodent model, we now report the first results of exploratory in vivo islet allograft studies in rats using locally delivered glucocorticoids (dexamethasone phosphate and the soft steroid loteprednol etabonate). Following in vitro assessments, in silico drug distribution models were used to establish tentative therapeutic dose ranges. Sustained local delivery was achieved via implantable osmotic mini-pumps through a central sprinkler, as well as with a sustained-delivery formulation for loteprednol etabonate using poly(D,L-lactic) acid (PLA) microspheres. Doses delivered locally were approximately hundred-fold smaller than those typically used in systemic treatments. While several solubility, stability, and implantation problems still remain to be addressed, both compounds showed promise in their ability to prolong graft survival after tapering of systemic immunosuppression, compared to control groups.
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PMID:Feasibility of localized immunosuppression: 1. Exploratory studies with glucocorticoids in a biohybrid device designed for cell transplantation. 2061 90

Vitamin D deficiency, diagnosed when the serum 25-hydroxyvitamin D (25-OHD(3)) concentration is less than 20 ng/mL, has joined vitamin A deficiency as two of the most common nutrition-responsive medical conditions worldwide. There have been more scientific articles published about vitamin D in the 21st century than about any other vitamin, reflecting the massive expansion of the field of vitamin D research. Adequate vitamin D status has been linked to decreased risks of developing specific cancers, including cancers of the esophagus, stomach, colon, rectum, gallbladder, pancreas, lung, breast, uterus, ovary, prostate, urinary bladder, kidney, skin, thyroid, and hematopoietic system (e.g., Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma); bacterial infections; rheumatoid arthritis; Crohn's disease; periodontal disease; multiple sclerosis; asthma; type 2 diabetes; cardiovascular disease; stroke; peripheral artery disease; hypertension; chronic kidney disease; muscle weakness; cognitive impairment; Alzheimer's disease; clinical depression; and premature death. On the other hand, inadequate vitamin D status during human pregnancy may be associated with increased risk for the development of type 1 diabetes in the offspring. However, this point of view may be excessively optimistic. There also is evidence that despite the current heavy reliance on serum 25-OHD(3) concentration for the diagnosis of an individual's vitamin D status, local tissue vitamin D intoxication may be present in individuals with much lower serum 25-OHD(3) concentrations than are currently appreciated. Only rarely are the symptoms of local tissue vitamin D intoxication associated with vitamin D status or intake. An individual's serum 25-OHD(3) concentration may appear to be "low" for reasons totally independent of sunlight exposure or vitamin D intake. Serum 25-OHD(3) concentration is only poorly responsive to increases in vitamin D intake, and the prolonged routine consumption of thousands of international units of vitamin D may interfere with the regulation of phosphate homeostasis by fibroblast growth factor-23 (FGF23) and the Klotho gene product, with consequences that are detrimental to human health. In light of these counterbalancing observations, curbing excessive enthusiasm for universally increasing vitamin D intake recommendations may be in order.
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PMID:Vitamin D: health panacea or false prophet? 2358 82