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A Potential Role of the Unfolded Protein Response in the Impaired Production and Release of Epinephrine in Recurrent Hypoglycemia

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE82145 | GEO | 2016/07/01

SECONDARY ACCESSION(S): PRJNA324140

REPOSITORIES: GEO

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A Potential Role of the Unfolded Protein Response in the Impaired Production and Release of Epinephrine in Recurrent Hypoglycemia

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

MicroRNA-7a overexpression in VMH restores the sympathoadrenal response to hypoglycemia

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

Whole genome expression profiling associates activation of unfolded protein response with impaired production and release of epinephrine after recurrent hypoglycemia.

Project description: Not available

| S-EPMC5325535 | biostudies-literature

Intermittent hypoxia inhibits epinephrine-induced transcriptional changes in human aortic endothelial cells

Project description:we investigated the effects of IH and epinephrine on gene expression in human aortic ECs using RNA-sequencing. We found a significant overlap between IH and epinephrine-induced differentially expressed genes (DEGs).

2022-09-05 | GSE205050 | GEO

Effect of high-dose epinephrine on myocardial gene set expression

Project description:Male and female mice were injected with NaCl vs epinephrine to induce acute paradoxical reversible heart failure akin to Takotsubo Syndrome with subsequent RNASeq analysis of left ventricular tissue.

2023-05-31 | E-MTAB-13031 | biostudies-arrayexpress

Gene expression profile at single nuclei level of brain tissues from diabetic mice exposed to acute or recurrent hypoglycemia.

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.

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Biological characterization of gene response to insulin-induced hypoglycemia in mouse retina

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.

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Project description:The importance of the impact of human hormones on commensal microbiota and microbial biofilms is established in lots of studies. In the present investigation, we studied the proteome of the biofilm matrix of the commensal actinobacterium Micrococcus luteus C01. In our investigation, we tested the effect of epinephrine in concentration 4.9×10-9 M on immature (24 h ) and mature (72 h) biofilms in comparison with controls without the hormone administration. We investigated the temporal changes in the matrix proteome during the incubation in control samples and in samples with epinephrine.

2022-09-20 | PXD035739 | Pride

Gene expression changes after epinephrine treated in breast cancer tumor cell

Project description:Chronic stress triggers activation of the sympathetic nervous system (SNS) and drives malignancy. Using an immunodeficient murine system, we show that chronic stress promotes breast cancer stem-like properties via lactate dehydrogenase A (LDHA) dependent metabolic rewiring. In this dataset, we used microarray to characterize the mRNA expression profiles from primary PBS and Epinephrine -treated MDA-MB-231 tumor cells.

2019-03-18 | GSE116781 | GEO

Repeated hypoglycemia in diabetic mice induce hypothalamic mitochondrial and synaptic activity deregulations characteristic of neurodegenerative diseases

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

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