Multi-organ single-cell RNA-sequencing of early hyperglycaemia responses
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE244475 | GEO | 2024/10/18
REPOSITORIES: GEO
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Project description:Immediate and early effects of transient hyperglycaemia were examined using fully- reversible transgenic diabetic mice. Transient hyperglycaemia altered expression of 769 arterial genes, of which 200 did not reverse following recovery from hyperglycaemia. Many such genes are known to promote atherogenesis, including several implicated in arterial calcification and inflammation. This supports the view that hyperglycaemia causes not only very early deleterious changes in arterial gene expression but that to a large extent these persist for some time after restoration of normal blood glucose levels in vivo. Together, results support the contention that avoiding excess CVD risk in diabetes requires very early correction of hyperglycaemia.
2010-08-09 | GSE15401 | GEO
Project description:People living with diabetes have an increased risk of developing active tuberculosis. The effects of diabetes (HbA1c ≥6.5%) and intermediate hyperglycaemia (HbA1c 5.7-6.5%), on this transcriptomic signature were investigated by RNA-seq, to enhance understanding of immunological susceptibility in diabetes-tuberculosis comorbidity.Diabetes increased the magnitude of gene expression change in the host transcriptome in tuberculosis, characterised by an increase in innate, and decrease in adaptive immune responses. Strikingly, patients with intermediate hyperglycaemia and tuberculosis exhibited blood transcriptomes much more similar to diabetes-tuberculosis patients than to uncomplicated tuberculosis patients. Aberrant transcriptomes unveil a susceptibility mechanism of DM patients to TB of enhanced inflammation and reduced interferon responses.
2020-07-16 | GSE114192 | GEO
Project description:Immediate and early effects of transient hyperglycaemia were examined using fully- reversible transgenic diabetic mice. Transient hyperglycaemia altered expression of 769 arterial genes, of which 200 did not reverse following recovery from hyperglycaemia. Many such genes are known to promote atherogenesis, including several implicated in arterial calcification and inflammation. This supports the view that hyperglycaemia causes not only very early deleterious changes in arterial gene expression but that to a large extent these persist for some time after restoration of normal blood glucose levels in vivo. Together, results support the contention that avoiding excess CVD risk in diabetes requires very early correction of hyperglycaemia. As shown previously (Pelengaris et al., 2002 Cell), c-MycERTAM protein is activated in pancreatic beta cells of adult transgenic mice, by daily intraperitoneal (IP) administration of tamoxifen (TAM; Sigma-Aldrich, Dorset, UK) (1 mg/0.2 ml in peanut oil). Inactivation of c-MycERTAM protein was achieved through withdrawal of TAM. Adult female mice, 3-6 months of age, inbred into CBA-C57Bl/6 background and maintained under barrier conditions, were treated with TAM for up to 7 days (Myc ‘ON’) and then monitored during recovery for more than 4 months (140 days) (Myc ‘OFF’). Experimental timepoints were: Days 2, 4 and 7: c-Myc ‘ON’; days 0, 11, 26: c-Myc ‘OFF’. Biological replicates: each timepoint included 3 biological replicates (n=3 mice).
2010-08-09 | E-GEOD-15401 | biostudies-arrayexpress
Project description:Immune dysfunction in intermediate hyperglycaemia and diabetes patients in tuberculosis
| PRJNA470512 | ENA
Project description:Diabetes mellitus (DM) is a disorder that disrupts the body from shifting glucose into the cells resulting in hyperglycaemia (1). Insulin dependence or DM that resembles type I diabetes in humans is commonly observed in dogs (2). Canine DM diagnosis is based on fasting hyperglycaemia and glucosuria with clinical presentation of polyuria, polydipsia, polyphagia and weight loss (2). Its treatment goal is blood glucose control, which can be accomplished through insulin therapy, dietary modification and control of concurrent disorders (3). The major complications of DM include diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy and atherosclerosis induced by chronic hyperglycaemia via several pathways (4). The proposed unifying mechanism that mediates the tissue-damaging effects of hyperglycaemia is superoxide overproduction (5). Effective monitoring is required for DM treatment to reduce the risk of progression and complication. Hence, the identification of novel biomarkers is being researched (6, 7). Proteomics has been recognised as an important tool for establishing a diagnosis of disease aetiology and monitoring therapy outcomes (8, 9). Proteomic patterns were applied to detect diabetes and complications, as well as to evaluate treatment effectiveness in humans (10-12). There is limited information on proteomic data in DM dogs (13-15). In a proteomic analysis of serum samples from DM dogs, most upregulated proteins are involved in oxidative state, defence and inflammation (13). Medicinal plants are utilised in DM dogs as an adjunct medicine in combination with standard treatment to prevent the development of long-term diabetes complications and improve overall well-being. Curcumin, the most phytochemically active curcuminoid extracted from Curcuma longa, has gained attention in human and laboratory animals. Curcumin is known to have antioxidant, anti-inflammatory and anticancer properties (16-18). In humans and experimental animals with DM, curcumin has an antioxidant potential of enhanced reduced glutathione (GSH) and reduced malondialdehyde (MDA) levels (19, 20). The anti-inflammatory effects of curcumin in DM were reported via decreased interleukin-1β (IL‐1β), interleukin-6 (IL‐6), interleukin-8 (IL‐8) and tumour necrosis factor-α levels and also diminished monocyte chemoattractant protein-1 and C-reactive protein levels (19-21). There has been no published evidence of the impact, safety and proteomic profiles of curcuminoids, particularly curcumin, in client-own DM dogs. Accordingly, the aims of the present study were (1) to evaluate the effects of curcuminoid supplementation on canine DM-associated oxidative stress and inflammation, (2) to determine the safety of curcuminoid supplementation in canine diabetes and (3) to determine whether curcuminoid has an impact on proteins implicated in DM-associated complications by a proteomic analysis.
2022-12-15 | PXD037667 | Pride
Project description:Effects of hyperglycaemia and genetic background differences on renal and hepatic gene expression
2009-07-01 | E-TABM-500 | biostudies-arrayexpress
Project description:AIMS/HYPOTHESIS: Pregnancies complicated by diabetes have a higher risk of adverse outcomes for mothers and children, including predisposition to disease later in life, such as metabolic syndrome and hypertension. We hypothesized that adverse outcomes from diabetic pregnancies may be linked to compromised placental function. Our goal in this study was to identify cellular and molecular abnormalities in diabetic placenta. METHODS: Using a mouse model of diabetic pregnancy, placental gene expression was assayed at midgestation and cellular composition was analyzed at various stages. Genome-wide expression profiling was validated by quantitative PCR, and tissue localization studies were performed to identify cellular correlates of altered gene expression in diabetic placenta. RESULTS: We detected significantly altered gene expression in diabetic placenta for genes expressed in the maternal as well as those in the embryonic compartments. We also found altered cellular composition of the decidual compartment. Furthermore, the junctional and labyrinth layers were reduced in diabetic placenta, accompanied by aberrant differentiation of spongiotrophoblast cells. CONCLUSIONS/INTERPRETATION: Diabetes during pregnancy alters transcriptional profiles in the murine placenta, affecting cells of both embryonic and maternal origin, and involving several genes not previously implicated in diabetic pregnancies. The molecular changes and abnormal differentiation of multiple cell types precede impaired growth of junctional zone and labyrinth, and placenta overall. Whether these changes represent direct responses to hyperglycaemia or physiological adaptations, they are likely to play a role in pregnancy complications and outcomes, and have implications for developmental origins of adult disease. The STZ diabetic mouse model was used to investigate gene expression changes in diabetic placentae at E10.5. Placentae were dissected from 5 different FVB dams at embryonic day 10.5 under diabetic conditions and from 5 control dams. Gene expression profiles from five individual placentae from independent pregnancies per group were compared.
2011-06-01 | E-GEOD-28277 | biostudies-arrayexpress
Project description:It has been well established that the presence of diabetes is accompanied by a chronic inflammatory state promoting various diabetes-associated complications. One potential driver of this enhanced inflammatory state in patients with diabetes is hyperglycemia. Even after blood glucose control is achieved, diabetes-associated complications persist, suggesting the presence of a “hyperglycemic memory.” Innate immune cells, critically involved in various complications associated with diabetes, can build nonspecific, immunological memory (trained immunity) via epigenetic regulation. We examine the potential involvement of hyperglycemia-induced trained immunity in promoting inflammation. Our results show that hyperglycemia induces a trained phenotype in vivo in mice and in vitro in human monocytes, representative by an increased TNF-a secretion after ex vivo stimulation with LPS. These effects were largely mediated by epigenetic changes controlled by the mixed lineage leukemia (MLL) family because treatment with the MLL inhibitor menin-MLL during the process of trained immunity acquisition repressed the proinflammatory phenotype. Collectively, our results identify a novel link between hyperglycemia and inflammation in innate immune cells that might explain the increased proinflammatory state during diabetes potentially contributing to the development of various diabetes-associated complications.
2021-01-07 | GSE164338 | GEO
Project description:We found a novel molecular link between hyperglycaemia and the increased frequency of aggressive prostate cancer. High glucose was demonstrated to increase the expression of miR-301a which targeted Smad4 and p21, resulted in promoting the proliferation of prostate cancer cells.
2016-01-22 | GSE77092 | GEO
Project description:Effects of hyperglycaemia and genetic background differences on renal and hepatic gene expression
2009-06-03 | E-TABM-502 | biostudies-arrayexpress