Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Biosynthesis of H2S is impaired in non-obese diabetic (NOD) mice.

ABSTRACT: BACKGROUND AND PURPOSE: Hydrogen sulphide (H2S) has been involved in cardiovascular homoeostasis but data about its role in animal models of diabetic pathology are still lacking. Here, we have analysed H2S signalling in a genetic model of diabetes, the non-obese diabetic (NOD) mice. EXPERIMENTAL APPROACH: NOD mice exhibit a progressive endothelial dysfunction characterized by a reduced reactivity of blood vessels as diabetes develops. NOD mice were divided into three groups according to different glycosuria values: NOD I, NOD II and NOD III. Age-matched non-obese resistant (NOR) mice were used as controls. H(2)S levels in plasma and aortic tissue were measured. Functional studies in aorta were carried out in isolated organ baths using both an exogenous source of H2S (NaHS) and the metabolic precursor (L-cysteine). Real time PCR and western blot analysis were also carried out on aortic tissues. KEY RESULTS: NOD mice exhibited a progressive reduction of H2S plasma levels, which paralleled disease severity. L-cysteine-induced H2S production by aortic tissues was also progressively reduced. L-cysteine-induced vasorelaxation was significantly reduced in NOD mice while NaHS-induced relaxation was unaffected. ODQ (guanylate cyclase inhibitor), L-NAME (NO synthase inhibitor) or PAG, an inhibitor of cystathionine-gamma-lyase (CSE) inhibited H2S production induced by L-cysteine. CONCLUSIONS AND IMPLICATIONS: In NOD mice, endogenous H2S production is significantly impaired. Also, the ability of isolated aorta to respond to exogenous H2S is enhanced and endothelium-derived NO appears to be involved in the enzymatic conversion of L-cysteine into H2S.

SUBMITTER: Brancaleone V

PROVIDER: S-EPMC2584926 | biostudies-other | 2008 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Genetic Analysis of Substrain Divergence in Non-Obese Diabetic (NOD) Mice.

Project description:The non-obese diabetic (NOD) mouse is a polygenic model for type 1 diabetes that is characterized by insulitis, a leukocytic infiltration of the pancreatic islets. During ~35 years since the original inbred strain was developed in Japan, NOD substrains have been established at different laboratories around the world. Although environmental differences among NOD colonies capable of impacting diabetes incidence have been recognized, differences arising from genetic divergence have not been analyzed previously. We use both mouse diversity array and whole-exome capture sequencing platforms to identify genetic differences distinguishing five NOD substrains. We describe 64 single-nucleotide polymorphisms, and two short indels that differ in coding regions of the five NOD substrains. A 100-kb deletion on Chromosome 3 distinguishes NOD/ShiLtJ and NOD/ShiLtDvs from three other substrains, whereas a 111-kb deletion in the Icam2 gene on Chromosome 11 is unique to the NOD/ShiLtDvs genome. The extent of genetic divergence for NOD substrains is compared with similar studies for C57BL6 and BALB/c substrains. As mutations are fixed to homozygosity by continued inbreeding, significant differences in substrain phenotypes are to be expected. These results emphasize the importance of using embryo freezing methods to minimize genetic drift within substrains and of applying appropriate genetic nomenclature to permit substrain recognition when one is used.

| S-EPMC4426365 | biostudies-literature

Regulation of contact sensitivity in non-obese diabetic (NOD) mice by innate immunity.

Project description:BACKGROUND:Genetic background influences allergic immune responses to environmental stimuli. Non-obese diabetic (NOD) mice are highly susceptible to environmental stimuli. Little is known about the interaction of autoimmune genetic factors with innate immunity in allergies, especially skin hypersensitivity. OBJECTIVES:To study the interplay of innate immunity and autoimmune genetic factors in contact hypersensitivity (CHS) by using various innate immunity-deficient NOD mice. METHODS:Toll-like receptor (TLR) 2-deficient, TLR9-deficient and MyD88-deficient NOD mice were used to investigate CHS. The cellular mechanism was determined by flow cytometry in vitro and adoptive cell transfer in vivo. To investigate the role of MyD88 in dendritic cells (DCs) in CHS, we also used CD11cMyD88+ MyD88-/- NOD mice, in which MyD88 is expressed only in CD11c+ cells. RESULTS:We found that innate immunity negatively regulates CHS, as innate immunity-deficient NOD mice developed exacerbated CHS accompanied by increased numbers of skin-migrating CD11c+ DCs expressing higher levels of major histocompatibility complex II and CD80. Moreover, MyD88-/- NOD mice had increased numbers of CD11c+ CD207- CD103+ DCs and activated T effector cells in the skin-draining lymph nodes. Strikingly, re-expression of MyD88 in CD11c+ DCs (CD11cMyD88+ MyD88-/- NOD mice) restored hyper-CHS to a normal level in MyD88-/- NOD mice. CONCLUSION:Our results suggest that the autoimmune-prone NOD genetic background aggravates CHS regulated by innate immunity, through DCs and T effector cells.

| S-EPMC6126938 | biostudies-literature

Endometrial receptivity defects and impaired implantation in diabetic NOD mice.

Project description:Implantation failure is a major hurdle to a successful pregnancy. The high rate of postimplantation fetal loss in nonobese diabetic (NOD) mice is believed to be related to an abnormal decidual production of interferon (IFN)gamma. To address whether diabetes alters the natural events associated with successful implantation, certain morphological and molecular features of uterine receptivity in diabetic NOD (dNOD) mice were examined in normally mated pregnancy and in concanavalin A (ConA)-induced pseudopregnancy. As opposed to normoglycemic NOD (cNOD) mice, dNOD mice expressed retarded maturation of their uterine pinopodes and overexpressed MUC1 mucin at implantation sites (P < 0.001). Uterine production of leukemia inhibitory factor (LIF) and phosphorylation of uterine NFkappaBp65 and STAT3-Ty705 were found to be low (P < 0.01) during Day 4.5 postcoitum, whereas IFNgamma was aberrantly overexpressed. Loss of temporal regulation of progesterone receptor A (PR A) and PR B, together with aberrantly increased expression of the protein inhibitor of activated STAT-y (PIASy) (P < 0.01) and reduced recruitment (P < 0.01) of the latter to nuclear progesterone receptor sites were prominent features of decidualization failure occurring at peri-implantation in dNOD mice. In conclusion, the aberrant expression of endometrial IFNgamma in dNOD mice is associated with a nonreceptive endometrial milieu contributing to peri-implantation embryo loss in type 1 diabetes.

| S-EPMC3726408 | biostudies-literature

Sex-dependent effects of bisphenol A on type 1 diabetes development in non-obese diabetic (NOD) mice.

Project description:Type 1 diabetes (T1D) is an autoimmune disease caused by immune-mediated pancreatic ?-cell destruction. The endocrine disrupting chemical bisphenol A (BPA) has widespread human exposure and can modulate immune function and the gut microbiome (GMB), which may contribute to the increasing T1D incidence worldwide. It was hypothesized that BPA had sex-dependent effects on T1D by modulating immune homeostasis and GMB. Adult female and male non-obese diabetic (NOD) mice were orally administered BPA at environmentally relevant doses (30 or 300 µg/kg). Antibiotic-treated adult NOD females were exposed to 0 or 30 µg/kg BPA. BPA accelerated T1D development in females, but delayed males from T1D. Consistently, females had a shift towards pro-inflammation (e.g., increased macrophages and Bacteroidetes), while males had increases in anti-inflammatory immune factors and a decrease in both anti- and pro-inflammatory GMB. Although bacteria altered during sub-acute BPA exposure differed from bacteria altered from chronic BPA exposure in both sexes, the GMB profile was consistently pro-inflammatory in females, while males had a general decrease of both anti- and pro-inflammatory gut microbes. However, treatment of females with the antibiotic vancomycin failed to prevent BPA-induced glucose intolerance, suggesting changes in Gram-positive bacteria were not a primary mechanism. In conclusion, BPA exposure was found to have sex dimorphic effects on T1D with detrimental effects in females, and immunomodulation was identified as the primary mechanism.

| S-EPMC6511313 | biostudies-literature

Paquinimod prevents development of diabetes in the non-obese diabetic (NOD) mouse.

Project description:Quinoline-3-carboxamides (Q compounds) are immunomodulatory compounds that have shown efficacy both in autoimmune disease and cancer. We have in here investigated the impact of one such compound, paquinimod, on the development of diabetes in the NOD mouse model for type I diabetes (T1D). In cohorts of NOD mice treated with paquinimod between weeks 10 to 20 of age and followed up until 40 weeks of age, we observed dose-dependent reduction in incidence of disease as well as delayed onset of disease. Further, in contrast to untreated controls, the majority of NOD mice treated from 15 weeks of age did not develop diabetes at 30 weeks of age. Importantly, these mice displayed significantly less insulitis, which correlated with selectively reduced number of splenic macrophages and splenic Ly6Chi inflammatory monocytes at end point as compared to untreated controls. Collectively, these results demonstrate that paquinimod treatment can significantly inhibit progression of insulitis to T1D in the NOD mouse. We propose that the effect of paquinimod on disease progression may be related to the reduced number of these myeloid cell populations. Our finding also indicates that this compound could be a candidate for clinical development towards diabetes therapy in humans.

| S-EPMC5942776 | biostudies-literature

Structure modeling and antidiabetic activity of a seed protein of Momordica charantia in non-obese diabetic (NOD) mice.

Project description:Momordica charantia is a well known medicinal plant used in the traditional medicinal system for the treatment of various diseases including diabetes mellitus. Recently, a novel protein termed as ADMc1 from the seed extract of M. charantia has been identified and isolated showing significant antihyperglycemic activity in type 1 diabetic rats in which diabetes was induced. However, the structure of this protein has not yet been analyzed. Homology modeling approach was used to generate a high quality protein 3D structure for the amino acid sequence of the ADMc1 protein in this study. The comparative assessment of secondary structures revealed ADMc1 as an all-alpha helix protein with random coils. Tertiary structure predicted on the template structure of Napin of B. Napus (PDB ID: 1SM7) with which the ADMc1 showed significant sequence similarity, was validated using protein structure validation tools like PROCHECK, WHAT_CHECK, VERIFY3D and ProSA. Arrangement of disulfide bridges formed by cysteine residues were predicted by the Dianna 1.1 server. The presence of multiple disulfide bond confers the stable nature of the ADMc1 protein. Further, the biological activity of the ADMc1 was assessed in non-obese diabetic (NOD) mice which are spontaneous model of type 1 diabetes. Significant reduction in the blood glucose levels of NOD mice was observed up to 8 h post administration of the rADMc1 protein. Overall, the structural characterizations with antihyperglycemic activity of this seed protein of Momordica charantia demonstrate its potential as an antidiabetic agent.

| S-EPMC3766308 | biostudies-literature

A gluten-free diet lowers NKG2D and ligand expression in BALB/c and non-obese diabetic (NOD) mice.

Project description:The interplay between diet and immune parameters which could affect type 1 diabetes (T1D) pathogenesis is not sufficiently clarified. Intestinal up-regulation of the activating receptor natural killer group 2D (NKG2D) (CD314) and its ligands is a hallmark of coeliac disease. However, the direct effect of gluten on NKG2D expression is not known. We studied, by fluorescence activated cell sorter (lymphoid tissues) and reverse transcription-quantitative polymerase chain reaction (intestine and pancreatic islets), if a gluten-free diet (GF diet) from 4 weeks of age or a gluten-free diet introduced in breeding pairs (SGF diet), induced changes in NKG2D expression on DX5(+) (CD49b) natural killer (NK) cells, CD8(+) T cells and in intestinal and islet levels of NKG2D and ligands in BALB/c and non-obese diabetic (NOD) mice. Gluten-free NOD mice had lower insulitis (P < 0·0001); reduced expression of NKG2D on DX5(+) NK cells in spleen and auricular lymph nodes (P < 0·05); and on CD8(+) T cells in pancreas-associated lymph nodes (P = 0·04). Moreover, the level of CD71 on DX5(+) NK cells and CD8(+) T cells (P < 0·005) was markedly reduced. GF and SGF mice had reduced expression of NKG2D and DX5 mRNA in intestine (P < 0·05). Differences in intestinal mRNA expression were found in mice at 8, 13 and 20 weeks. Intestinal expression of NKG2D ligands was reduced in SGF mice with lower expression of all ligands. In isolated islets, a SGF diet induced a higher expression of specific NKG2D ligands. Our data show that a gluten-free diet reduces the level of NKG2D and the expression of NKG2D ligands. These immunological changes may contribute to the lower T1D incidence associated with a gluten-free diet.

| S-EPMC4226590 | biostudies-literature

Knockout of the Amino Acid Transporter SLC6A19 and Autoimmune Diabetes Incidence in Female Non-Obese Diabetic (NOD) Mice.

Project description:High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the Slc6a19 gene encoding the system B(0) neutral amino acid transporter AT1 would reduce the incidence or delay the onset of type 1 diabetes in female NOD mice. Slc6a19 gene deficient NOD mice were generated using the CRISPR-Cas9 system which resulted in marked aminoaciduria. The incidence of diabetes by week 30 was 59.5% (22/37) and 69.0% (20/29) in NOD.Slc6a19+/+ and NOD.Slc6a19-/- mice, respectively (hazard ratio 0.77, 95% confidence interval 0.41-1.42; Mantel-Cox log rank test: p = 0.37). The median survival time without diabetes was 28 and 25 weeks for NOD.Slc6a19+/+ and NOD.Slc6a19-/- mice, respectively (ratio 1.1, 95% confidence interval 0.6-2.0). Histological analysis did not show differences in islet number or the degree of insulitis between wild type and Slc6a19 deficient NOD mice. We conclude that Slc6a19 deficiency does not prevent or delay the development of type 1 diabetes in female NOD mice.

| S-EPMC8540324 | biostudies-literature

Female MRL/lpr and Non-Obese Diabetic (NOD) Mice Treated with Placebo or Testosterone.

Project description:The Influence of Testosterone on Lacrimal Gland Gene Expression in Female Mice of the MRL/lpr and Non-obese Diabetic Models of SjšgrenÕs Syndrome Keywords: Placebo versus Testosterone Treatment.

2009-02-01 | GSE5877 | GEO

Female and Male Mice from the MRL/lpr and Non-Obese Diabetic (NOD) Strains.

Project description:The Effect of Sex on Lacrimal Gland Gene Expression in the MRL/lpr and Non-obese Diabetic Mouse Models of SjšgrenÕs Syndrome Keywords: Female vs Male Lacrimal Gland Gene Expression.

2009-02-01 | GSE5876 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data