Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Peripheral Insulin Regulates A Broad Network of Gene Expression in Brain

ABSTRACT: The brain is now recognized as an insulin sensitive tissue, however, the role of insulin on gene expression in the brain is largely unknown. Here, we show that increases in peripheral insulin within the physiological range regulate expression of a broad network of gene expression, with the most robust effect in the hypothalamus followed by the hippocampus then nucleus accumbens. In hypothalamus, insulin regulates many genes involved in neurotransmission, including up-regulating expression of GABA-A receptor components, differentially modulating glutamate receptors, and suppressing multiple neuropeptides. Insulin also strongly modulates brain metabolism by suppressing genes involved in the glycolysis and pentose phosphate pathways while increasing expression of genes regulating pyruvate dehydrogenase complex, long-chain fatty acyl-CoA and cholesterol biosynthesis, rerouting carbon substrates to the biogenesis of plasma membrane for neuronal and glial function and synaptic remodeling. Thus, peripheral insulin acutely and potently regulates expression of genes involved in neurotransmission, neuromodulation and brain metabolism.

ORGANISM(S): Mus musculus

PROVIDER: GSE132352 | GEO | 2021/06/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Diabetes and Insulin in Regulation of Brain Cholesterol Metabolism

Project description:The brain is the most cholesterol-rich organ in the body, most of which comes from in situ synthesis. Here we demonstrate that in insulin-deficient diabetic mice, there is a reduction in expression of the major transcriptional regulator of cholesterol metabolism, SREBP-2, and its downstream genes in the hypothalamus and other areas of the brain, leading to a reduction in brain cholesterol synthesis and synaptosomal cholesterol content. These changes are due, at least in part, to direct effects of insulin to regulate these genes in neurons and glial cells and can be corrected by intracerebroventricular injections of insulin. Knockdown of SREBP-2 in cultured neurons causes a decrease in markers of synapse formation and reduction of SREBP-2 in the hypothalamus of mice using shRNA results in increased feeding and weight gain. Thus, insulin and diabetes can alter brain cholesterol metabolism, and this may play an important role in the neurologic and metabolic dysfunction observed in diabetes and other disease states. Hypothalamus was compared between streptozotocin (STZ)-induced diabetic, ob/ob, and control mice, with 5-6 replicates per goup.

2014-10-03 | E-GEOD-62013 | biostudies-arrayexpress

Diabetes and Insulin in Regulation of Brain Cholesterol Metabolism

2014-10-03 | GSE62013 | GEO

SMN deficiency perturbs monoamine neurotransmitter metabolism in spinal muscular atrophy

Project description:<p>Beyond motor neuron degeneration, homozygous mutations in the survival motor neuron 1 (SMN1) gene cause multiorgan and metabolic defects in patients with spinal muscular atrophy (SMA). However, the precise biochemical features of these alterations and the age of onset in the brain and peripheral organs remain unclear. Using untargeted NMR-based metabolomics in SMA mice, we identify cerebral and hepatic abnormalities related to energy homeostasis pathways and amino acid metabolism, emerging already at postnatal day 3 (P3) in the liver. Through HPLC, we find that SMN deficiency induces a drop in cerebral norepinephrine levels in overt symptomatic SMA mice at P11, affecting the mRNA and protein expression of key genes regulating monoamine metabolism, including aromatic L-amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DβH) and monoamine oxidase A (MAO-A). In support of the translational value of our preclinical observations, we also discovered that SMN upregulation increases cerebrospinal fluid norepinephrine concentration in Nusinersen-treated SMA1 patients. Our findings highlight a previously unrecognized harmful influence of low SMN levels on the expression of critical enzymes involved in monoamine metabolism, suggesting that SMN-inducing therapies may modulate catecholamine neurotransmission. These results may also be relevant for setting therapeutic approaches to counteract peripheral metabolic defects in SMA. </p>

2023-11-27 | MTBLS8784 | MetaboLights

profiling of hypothalamus from mice s.c. injected with 4T-1 mammary carcinoma cells vs. PBS

Project description:The main function of the nervous system is to maintain homeostasis by sensing and reacting to signals that reach a certain threshold. For example, the brain can sense immune peripheral events through soluble compounds or the vagus nerve and can react through activation of the hypothalamus-pituitary-adrenal axis, resulting in the modulation of an ongoing immune response. Cancer progression is characterized by high mutation rates, with each mutation potentially promoting alarm signals during the 10 to 15 years of cancer development before clinical detection. It is not known, however, whether the brain can recognize the presence of a peripheral tumour, and if this recognition can be molecularly assessed. Using genome-wide expression analysis in a model of mammary carcinoma, we show that a tumor growing at the periphery can indeed promote changes in the expression levels of defined sets of genes in the hypothalamus. These changes occur as early as 18 h after tumour cell injection and involve specific signalling pathways. These findings prove that cancer-derived signals are effective in eliciting specific changes in gene expression in discrete brain regions and open a question regarding the potential role of brain genes in cancer outcomes. Keywords: gene expression profile of the hypothalamus in response to peripheral tumor cells

2007-05-02 | GSE7296 | GEO

profiling of hypothalamus from mice s.c. injected with LL/2(LLC1) lung carcinoma cells vs. PBS

Project description:The main function of the nervous system is to maintain homeostasis by sensing and reacting to signals that reach a certain threshold 1-5. For example, the brain can sense immune peripheral events through soluble compounds or the vagus nerve and can react through activation of the hypothalamus-pituitary-adrenal axis, resulting in the modulation of an ongoing immune response. Cancer progression is characterized by high mutation rates, with each mutation potentially promoting alarm signals during the 10 to 15 years of cancer development before clinical detection. It is not known, however, whether the brain can recognize the presence of a peripheral tumour, and if this recognition can be molecularly assessed. Using genome-wide expression analysis in a model of lung carcinoma, we show that a tumor growing at the periphery can indeed promote changes in the expression levels of defined sets of genes in the hypothalamus. These changes occur as early as 18 h after tumour cell injection and involve specific signalling pathways. These findings prove that cancer-derived signals are effective in eliciting specific changes in gene expression in discrete brain regions and open a question regarding the potential role of brain genes in cancer outcomes Keywords: gene expression profile of the hypothalamus in response to peripheral tumor cells

2007-05-02 | GSE7295 | GEO

profiling of hypothalamus from mice s.c. injected with CT-26wt colon carcinoma cells vs. PBS

Project description:The main function of the nervous system is to maintain homeostasis by sensing and reacting to signals that reach a certain threshold. For example, the brain can sense immune peripheral events through soluble compounds or the vagus nerve and can react through activation of the hypothalamus-pituitary-adrenal axis, resulting in the modulation of an ongoing immune response. Cancer progression is characterized by high mutation rates, with each mutation potentially promoting alarm signals during the 10 to 15 years of cancer development before clinical detection. It is not known, however, whether the brain can recognize the presence of a peripheral tumour, and if this recognition can be molecularly assessed. Using genome-wide expression analysis in a model of colon carcinoma, we show that a tumor growing at the periphery can indeed promote changes in the expression levels of defined sets of genes in the hypothalamus. These changes occur as early as 18 h after tumour cell injection and involve specific signalling pathways. These findings prove that cancer-derived signals are effective in eliciting specific changes in gene expression in discrete brain regions and open a question regarding the potential role of brain genes in cancer outcomes. Keywords: gene expression profile of the hypothalamus in response to peripheral tumor cells

2007-05-02 | GSE7294 | GEO

Peripheral Insulin Regulates A Broad Network of Gene Expression in Brain

Project description:Peripheral Insulin Regulates A Broad Network of Gene Expression in Brain

| PRJNA547673 | ENA

Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition

Project description:Global energy balance in mammals is controlled by the actions of circulating hormones that coordinate fuel production and utilization in metabolically active tissues. Bone-derived osteocalcin, in its undercarboxylated, hormonal form, regulates fat deposition and is a potent insulin secretagogue. Here, we show that insulin receptor (IR) signaling in osteoblasts controls osteoblast development and osteocalcin expression by suppressing the Runx2 inhibitor Twist-2. Mice lacking IR in osteoblasts have low circulating undercarboxylated osteocalcin and reduced bone acquisition due to decreased bone formation and deficient numbers of osteoblasts. With age, these mice develop marked peripheral adiposity and hyperglycemia accompanied by severe glucose intolerance and insulin resistance. The metabolic abnormalities in these mice are improved by infusion of exogenous under-carboxylated osteocalcin. These results indicate the existence of a bone-pancreas endocrine loop through which insulin signaling in the osteoblast ensures osteoblast differentiation and stimulates osteocalcin production, which in turn regulates insulin sensitivity and pancreatic insulin secretion to control glucose homeostasis. We used microarrays to detail the global gene expression changes in response to insulin acting through insulin receptor in osteoblasts and identified distinct genes specifically involved in bone remodeling process. 4 groups and 3 time points (0h as a control, 6h, 12h, and 24h)

2010-05-27 | E-GEOD-21710 | biostudies-arrayexpress

Brain adiponectin signaling controls peripheral insulin response in Drosophila

Project description:The brain plays a key role in energy homeostasis, detecting circulating hormones from peripheral organs, nutrients, and metabolites, and integrating this information to control food intake and energy expenditure. However, the signals mediating communication between peripheral organs and brain are largely unknown. Here, we show that a group of neurons in the Drosophila larval brain expressing the adiponectin receptor (AdipoR) control systemic growth and metabolism. We identify glucose-regulated protein 78 (Grp78) as a circulating ligand for AdipoR. Grp78 is produced by fat cells in response to dietary sugar and modulates the activity of AdipoR-positive neurons. The terpenoid juvenile hormone (JH) serves as an effector for brain AdipoR signaling, reducing the levels of insulin signaling in peripheral organs. In conclusion, we identify a neuroendocrine axis whereby AdipoR neurons control systemic insulin responses by modulating peripheral JH function.

2021-06-15 | PXD013689 | Pride

Choroid Plexus-Derived Insulin Inhibits Feeding via Direct Signaling through Arcuate Nucleus

Project description:The choroid plexus is an important source of trophic factors for the developing and mature brain. Recently we described the expression and production of mature insulin in epithelial cells of the choroid plexus, and how its secretion can be modulated by serotonin through Htr2c, a metabotropic receptor that signals via Gq. To understand the function of this choroid plexus-derived insulin, here we describe a way to genetically target epithelial cells of the choroid plexus using a viral vector. With this, we modulated insulin expression and evaluated behavior. Insulin overexpression in the choroid plexus of wild type mice led to an inhibition in feeding, whereas insulin knockdown in choroid plexus of Ins1-/-Ins2fl/fl mice promoted discrete increases in food intake, especially after a period of fasting. Insulin overexpression in choroid plexus induced roust transcriptomic changes in the hypothalamus, most of which related to axonal growth and synapse-related processes. Finally, activation of Gq signaling in insulin-overexpressing choroid plexuses led to acute AKT phosphorylation in neurons of the arcuate nucleus, suggesting a direct action, through the CSF, of choroid plexus-derived insulin on the hypothalamus. Taken together our findings prove that the choroid plexus is a relevant source of insulin in the central nervous system, with physiological implications in feeding behavior. We believe that choroid plexus-derived insulin has to be taken into consideration in future work pertaining insulin actions in the brain.

2022-12-15 | GSE218188 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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