Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA324140 | ENA |
REPOSITORIES: ENA
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Project description:In order to gain further insight into the molecular mechanism(s) mediating the blunted epinephrine responses following recurrent hypoglycemia we utilized global gene expression profiling approach. Our results indicate the association between defective counterregulation (impaired epinephrine release) and the activation of the unfolded protein response as well as increased neuropeptide signaling, altered ion homeostasis and downregulation of proteins involved in Ca2+-dependent exocytosis of secretory vesicles. We compared the entire transcriptomes during recurrent (defective CRR model, 2RH) and acute hypoglycemia (normal CRR group, 2RS) in the adrenal medulla of normal Sprague-Dawley rats.
2016-07-01 | E-GEOD-82145 | biostudies-arrayexpress
Project description:In order to gain further insight into the molecular mechanism(s) mediating the blunted epinephrine responses following recurrent hypoglycemia we utilized global gene expression profiling approach. Our results indicate the association between defective counterregulation (impaired epinephrine release) and the activation of the unfolded protein response as well as increased neuropeptide signaling, altered ion homeostasis and downregulation of proteins involved in Ca2+-dependent exocytosis of secretory vesicles.
2016-07-01 | GSE82145 | GEO
Project description:It is proposed that the impaired sympathoadrenal response to hypoglycemia induced by recurrent insulin-induced hypoglycemia (RH) is an adaptive phenomenon induced by specific changes in microRNA expression in the ventromedial hypothalamus (VMH). To test this hypothesis, genome-wide microRNAomic profiling of the VMH by RNA-sequencing was performed in control and RH treated rats. Differential expression analysis identified microRNA-7a-5p and microRNA-665 as potential mediators of this phenomenon. To further test this hypothesis, experiments were conducted consisting of targeted lentiviral-mediated overexpression of microRNA-7a-5p and downregulation of microRNA-665 in the VMH. Hyperinsulinemic hypoglycemic clamp experiments demonstrated that targeted overexpression of microRNA-7a-5p (but not downregulation of microRNA-665) in the VMH of RH rats restored the epinephrine response to hypoglycemia. This restored response to hypoglycemia was associated with a restoration of GABAA receptor gene expression. Finally, a direct interaction of microRNA-7a-5p with 3’-UTR of GABAA receptor α1-subunit (Gabra1) gene was demonstrated in a luciferase assay. These findings indicate that 1) the impaired sympathoadrenal response induced by RH is associated with changes in VMH microRNA expression, and 2) microRNA-7a-5p, possibly via direct downregulation of GABA receptor gene expression, may serve as a mediator of the altered sympathoadrenal response to hypoglycemia.
2019-10-17 | GSE138472 | GEO
Project description:Repeated exposures to insulin-induced hypoglycemia in diabetic patients progressively impair the counter-regulatory response (CRR) that restores normoglycemia. This defect is characterized by reduced secretion of glucagon and other counter-regulatory hormones. Evidence indicates that glucose responsive neurons located in the hypothalamus, orchestrate the CRR. Here, we aimed at identifying the changes in hypothalamic gene and protein expression that underlie impaired CRR. High fat diet fed and low dose streptozocin-treated C57BL6N mice were exposed to one (acute hypoglycemia, AH) or multiple (recurrent hypoglycemia, RH) insulin-induced hypoglycemic episodes. Single nuclei RNA sequencing (snRNAseq) data were obtained from the hypothalamus and cortex of AH and RH mice. Proteomic data were also obtained from hypothalamic synaptosomal fractions. The present study shows that repeated moderate hypoglycemia in diabetic mice lead, in the hypothalamus, to multiple cellular physiology changes, affecting all cell types and their interactions, which show striking features of neurodegenerative diseases. It also shows that repeated hypoglycemic episodes affect very differently the hypothalamus and the cortex.
2023-11-13 | PXD040183 | Pride
Project description:The brain is an important controller of glucose homeostasis and mediates counterregulatory responses to hypoglycemia. We used single-nuclei transcriptomics to study the mechanisms of defective hypoglycaemia counter-regulation in brain in a model of diabetic mice exposed to acute or recurrent hypoglycemia.
2023-10-02 | GSE226277 | GEO
Project description:Hypoglycemia is a clinical hallmark of severe malaria, the often-lethal outcome of Plasmodium falciparum infection. Yet, the underlying mechanisms driving the pathogenesis of malaria-associated hypoglycemia remain poorly understood. Here we report that labile heme, an alarmin generated as a byproduct of hemolysis during the blood stage of Plasmodium spp. infection, plays a central role in the development of malaria-associated hypoglycemia. Labile heme recapitulated the hypometabolic response to Plasmodium (chabaudi chabaudi; Pcc) infection in mice, including the development of anorexia, transcriptional repression of hepatic glucose production (HGP) and reduction of glycemia, energy expenditure (EE) as well as core body temperature. While this hypometabolic response is protective against immune-mediated liver damage and anemia, when sustained over time it can lead to hypoglycemia and compromise EE as well as thermoregulation. In response, asexual stages of Plasmodium spp. activate a transcriptional program that reduces virulence in favor of sexual commitment and presumably malaria transmission. In conclusion, malaria-associated hypoglycemia represents a trade-off of a hypometabolic defense strategy against Plasmodium infection.
2021-12-31 | E-MTAB-10935 | biostudies-arrayexpress
Project description:Hypoglycemia is a clinical hallmark of severe malaria, the often-lethal outcome of Plasmodium falciparum infection. Yet, the underlying mechanisms driving the pathogenesis of malaria-associated hypoglycemia remain poorly understood. Here we report that labile heme, an alarmin generated as a byproduct of hemolysis during the blood stage of Plasmodium spp. infection, plays a central role in the development of malaria-associated hypoglycemia. Labile heme recapitulated the hypometabolic response to Plasmodium (chabaudi chabaudi; Pcc) infection in mice, including the development of anorexia, transcriptional repression of hepatic glucose production (HGP) and reduction of glycemia, energy expenditure (EE) as well as core body temperature. While this hypometabolic response is protective against immune-mediated liver damage and anemia, when sustained over time it can lead to hypoglycemia and compromise EE as well as thermoregulation. I response, asexual stages of Plasmodium spp. activate a transcriptional program that reduces virulence in favor of sexual commitment and presumably malaria transmission. In conclusion, malaria-associated hypoglycemia represents a trade-off of a hypometabolic defense strategy against Plasmodium infection.
2021-12-31 | E-MTAB-10939 | biostudies-arrayexpress
Project description:Glucose is the most important metabolic substrate of the retina and maintenance of nor-moglycemia is an essential challenge for diabetic patients. Glycemic excursions could lead to cardiovascular disease, nephropathy, neuropathy and retinopathy. We recently showed that hy-poglycemia induced retinal cell death in mouse via caspase 3 activation and glutathione (GSH) decrease. Ex vivo experiments in 661W photoreceptor cells confirmed the low-glucose induction of death via superoxide production and activation of caspase 3, which was concomitant with a decrease of GSH content. We evaluate herein retinal gene expression 4 h and 48 h after insulin-induced hypoglycemia. Microarray analysis demonstrated clusters of genes whose expression is modified by hypoglycemia and we discuss the potential implication of those genes in retinal cell death. In addition, we highlight, by gene set enrichment analysis, three important pathways, including KEGG lysosomes, KEGG GSH metabolism and REACTOME apoptosis pathways. We tested the effect of recurrent hypoglycemia (three successive 5h periods of hypoglycemia separated by 48 h recovery) on retinal cell death. Interestingly, exposure to multiple hypoglycemic events prevents retinal cell death and GSH decrease, or adapts the retina to external stress by restoring GSH level comparable to control situation. We hypothesize that scavenger GSH is a key compound in this apoptotic process, and maintaining “normal” GSH level, as well as a strict glycemic control, may represent a therapeutic challenge in order to avoid side effects of diabetes, especially diabetic retinopathy.
2017-01-03 | GSE67523 | GEO
Project description:Postprandial hypoglycemia is a disabling complication of bariatric surgery. So far, no therapy exists, and the underlying mechanisms remain unclear. Here, we hypothesized that glucose-induced IL-1β leads to an exaggerated insulin response in this condition. Therefore, we conducted a placebo controlled, randomized, double-blind, cross-over study with the SGLT2-inhibitor empagliflozin (Jardiance [10mg]) and the IL-1 receptor antagonist anakinra (Kineret [100mg]). Both drugs reduced postprandial insulin release and prevented hypoglycemia. Moreover, analysis of monocytes taken from this patient population ex-vivo revealed a hyper-reactive inflammatory state in these cells. Our study proposes a role for glucose-induced IL-1β in postprandial hypoglycemia after bariatric surgery and suggests that SGLT2-inhibitors and IL-1 antagonism may improve this condition.
2020-03-19 | GSE132781 | GEO
Project description:The goal of this study is to determine the effect of mild / moderate hypoglycemia on brain metabolism. To achieve this goal insulin-treated diabetic rats will be subjected to recurrent mild / moderate hypoglycemia.
2015-08-06 | ST000252 | MetabolomicsWorkbench