Related Experiment Video
Updated: Jun 22, 2025
09:39
Establishing a Mouse Model of a Pure Small Fiber Neuropathy with the Ultrapotent Agonist of Transient Receptor Potential Vanilloid Type 1
Published on: February 13, 2018
9.5K
Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting
Ze-Yu Zhou1,2, Ji-Ying Wang3, Zhi-Xiao Li4
1State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China.
Summary
Lower branched-chain amino acid (BCAA) levels in diabetic neuropathic pain (DNP) patients worsen nerve pain. Supplementing BCAAs or inhibiting LAT1 transporter alleviates DNP symptoms, offering new therapeutic targets.
Area of Science:
- Metabolic pathways
- Neuroscience
- Diabetology
Background:
- Diabetic neuropathic pain (DNP) is a common diabetes complication causing significant morbidity.
- Distinct metabolic profiles may exist between DNP and type 2 diabetes mellitus (T2DM) without neuropathy.
Purpose of the Study:
- To investigate serum metabolite differences between DNP and T2DM patients.
- To elucidate the underlying mechanisms of DNP development related to branched-chain amino acids (BCAAs).
Main Methods:
- Comparative analysis of serum metabolites in DNP and T2DM patients.
- Utilized mouse models (HFD/STZ and db/db) to study BCAA effects on DNP.
- Employed RNA sequencing and proteomic analysis to identify molecular pathways.
- Investigated the role of L-type amino acid transporter 1 (LAT1) and Kv1.2 channels.
Main Results:
- DNP patients exhibited significantly lower serum BCAA levels compared to T2DM patients.
- BCAA deficiency exacerbated DNP symptoms in mouse models, while supplementation alleviated them.
- BCAA deficiency upregulated LAT1 expression via ATF4, leading to reduced Kv1.2 channel function and increased neuronal excitability.
- Inhibition of LAT1 with BCH ameliorated DNP symptoms in mice.
Conclusions:
- Reduced BCAA levels are a key metabolic feature distinguishing DNP from T2DM.
- The BCAA-LAT1-Kv1.2 pathway is crucial in the pathogenesis of DNP.
- Targeting LAT1 presents a potential therapeutic strategy for managing diabetic neuropathic pain.
Related Concept Videos
01:23Local Anesthetics: Mechanism of Action
2.2K
Local anesthetics (LAs) block sensory and motor impulses by inhibiting the sodium channels on the nerve cell membranes. This induces temporary loss of sensation, relieving pain in a specific body area.
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
2.2K
01:24Local Anesthetics: Differential Sensitivity of Nerve Fibers
807
Local anesthetics (LAs) block the sodium channels of nerve trunks, sensory nerve endings, and neuromuscular junctions. Although LAs can block all kinds of nerves, the sensitivity of nerve fibers differs according to nerve types and structures. LAs are known to block myelinated fibers faster than unmyelinated ones. Also, they block pain or sensory neurons at low concentrations without affecting the motor neurons involved in muscle contractions. This helps relieve labor pain without affecting the...
807
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
285
Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
285
01:19Ligand-gated Ion Channels
12.4K
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
12.4K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.2K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.2K
01:12Local Anesthetics: Adverse Effects
405
While local anesthetics are generally safe and well-tolerated, they can occasionally cause adverse effects that vary in severity. Local anesthetics can induce toxicity at two distinct levels. They can either produce local effects through direct contact with the neural elements or be absorbed into the bloodstream from the injection site, leading to systemic effects.
Once absorbed into the systemic circulation, local anesthetics can affect the organs that depend on the functioning of sodium...
Once absorbed into the systemic circulation, local anesthetics can affect the organs that depend on the functioning of sodium...
405