ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Insulin reveals Akt signaling as a novel regulator of norepinephrine transporter trafficking and norepinephrine homeostasis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 84 citations in OpenAlex.
- Xenon gas as a potential treatment for opioid use disorder, alcohol use disorder, and related disorders.Medical gas research · 2025Review
- Neuroprotective actions of norepinephrine in neurological diseases.Pflugers Archiv : European journal of physiology · 2024Review
- CUDC-907, a dual PI3K/histone deacetylase inhibitor, increases meta-iodobenzylguanidine uptake (Journal of translational medicine · 2023Article
- Translating in vitro CFTR rescue into small molecule correctors for cystic fibrosis using the Library of Integrated Network-based Cellular Signatures drug discovery platform.CPT: pharmacometrics & systems pharmacology · 2022Article
- Schizophrenia Hypothesis: Autonomic Nervous System Dysregulation of Fetal and Adult Immune Tolerance.Frontiers in systems neuroscience · 2022Article
- The ameliorative role of Physalis pubescens L. against neurological impairment associated with streptozotocin induced diabetes in rats.Metabolic brain disease · 2021Article
- Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals.Scientific reports · 2021Article
- Article
- Interactions between insulin and diet on striatal dopamine uptake kinetics in rodent brain slices.The European journal of neuroscience · 2019Article
- Citral, a Monoterpene Inhibits Adipogenesis Through Modulation of Adipogenic Transcription Factors in 3T3-L1 Cells.Indian journal of clinical biochemistry : IJCB · 2018Article
- Article
- CaJournal of chemical neuroanatomy · 2017Article
- In Silico Prediction of the Anti-Depression Mechanism of a Herbal Formula (Tiansi Liquid) Containing Morinda officinalis and Cuscuta chinensis.Molecules (Basel, Switzerland) · 2017Article
- Central Nervous System GLP-1 Receptors Regulate Islet Hormone Secretion and Glucose Homeostasis in Male Rats.Endocrinology · 2017Article
- Densin-180 Controls the Trafficking and Signaling of L-Type Voltage-Gated CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters.Pharmacological reviews · 2016Review
- Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex.Brain research · 2016Review
- Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels.Translational psychiatry · 2016Article
- Phentermine induces conditioned rewarding effects via activation of the PI3K/Akt signaling pathway in the nucleus accumbens.Psychopharmacology · 2016Article
- Norepinephrine transporter expression is inversely associated with glycaemic indices: a pilot study in metabolically diverse persons with overweight and obesity.Obesity science & practice · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Noradrenergic signaling in the CNS plays an essential role in circuits involving attention, mood, memory, and stress as well as providing pivotal support for autonomic function in the peripheral nervous system. The high-affinity norepinephrine (NE) transporter (NET) is the primary mechanism by which noradrenergic synaptic transmission is terminated. Data indicate that NET function is regulated by insulin, a hormone critical for the regulation of metabolism. Given the high comorbidity of metabolic disorders such as diabetes and obesity with mental disorders such as depression and schizophrenia, we sought to determine how insulin signaling regulates NET function and thus noradrenergic homeostasis. Here, we show that acute insulin treatment, through the downstream kinase protein kinase B (Akt), significantly decreases NET surface expression in mouse hippocampal slices and superior cervical ganglion neuron boutons (sites of synaptic NE release). In vivo manipulation of insulin/Akt signaling, with streptozotocin, a drug that induces a type 1-like diabetic state in mice, also results in aberrant NET function and NE homeostasis. Notably, we also demonstrate that Akt inhibition or stimulation, independent of insulin, is capable of altering NET surface availability. These data suggest that aberrant states of Akt signaling such as in diabetes and obesity have the potential to alter NET function and noradrenergic tone in the brain. Furthermore, they provide one potential molecular mechanism by which Akt, a candidate gene for mood disorders such as schizophrenia and depression, can impact brain monoamine homeostasis.
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