INS Protein (Insulin)

INS Protein (Insulin)

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">INS (Insulin)</th></tr>
<tr><td><b>Gene</b></td><td>[INS](/entities/ins)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[P01308](https://www.uniprot.org/uniprot/P01308)</td></tr>
<tr><td><b>PDB Structures</b></td><td>1ZEN, 3J5Q</td></tr>
<tr><td><b>Molecular Weight</b></td><td>6 kDa (processed), 51 kDa (proinsulin)</td></tr>
<tr><td><b>Subcellular Localization</b></td><td>Secreted, cytoplasm</td></tr>
<tr><td><b>Expression</b></td><td>Pancreatic β-cells, brain [neurons](/entities/neurons)</td></tr>
<tr><td><b>Function</b></td><td>Metabolic regulation, neurotrophic factor</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">179 edges</a></td>
</tr>
</table>
</div>

Overview

INS Protein (Insulin)

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">INS (Insulin)</th></tr>
<tr><td><b>Gene</b></td><td>[INS](/entities/ins)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[P01308](https://www.uniprot.org/uniprot/P01308)</td></tr>
<tr><td><b>PDB Structures</b></td><td>1ZEN, 3J5Q</td></tr>
<tr><td><b>Molecular Weight</b></td><td>6 kDa (processed), 51 kDa (proinsulin)</td></tr>
<tr><td><b>Subcellular Localization</b></td><td>Secreted, cytoplasm</td></tr>
<tr><td><b>Expression</b></td><td>Pancreatic β-cells, brain [neurons](/entities/neurons)</td></tr>
<tr><td><b>Function</b></td><td>Metabolic regulation, neurotrophic factor</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">179 edges</a></td>
</tr>
</table>
</div>

Overview

Insulin is a peptide hormone encoded by the [INS](/genes/ins) gene, essential for glucose homeostasis and cellular energy metabolism. Produced by pancreatic β-cells, insulin acts as a key regulator of blood glucose levels and has critical roles in neuronal survival, synaptic plasticity, and cognitive function. The discovery of insulin signaling in the brain has revealed its importance beyond metabolic regulation, with growing evidence linking insulin dysfunction to neurodegenerative diseases, particularly [Alzheimer's disease](/diseases/alzheimers-disease).

Structure and Processing

Insulin is synthesized as a preprohormone (110 amino acids) in pancreatic β-cells and processed to proinsulin (86 amino acids). The mature insulin hormone consists of two polypeptide chains—A chain (21 amino acids) and B chain (30 amino acids)—connected by disulfide bonds. This processed form is stored in secretory granules and released in response to elevated blood glucose. The [INS](/genes/ins) gene is located on chromosome 11p15.5 and contains three exons encoding the preproinsulin peptide [1].

In the brain, insulin is produced locally by neurons and glia, and also transported across the [blood-brain barrier](/entities/blood-brain-barrier) via receptor-mediated transcytosis. Brain-derived insulin acts in an autocrine and paracrine manner, influencing neuronal function through insulin receptors (IR) expressed throughout the central nervous system, particularly in the [hippocampus](/brain-regions/hippocampus), [cortex](/brain-regions/cortex), and hypothalamus [2].

Insulin Signaling in the Brain

Receptor Expression

Neurons express both insulin receptor isoforms (IR-A and IR-B), with IR-A predominating in the brain. Insulin receptors are widely distributed in regions associated with learning and memory, including the hippocampus and prefrontal cortex. The receptor is a tyrosine kinase that autophosphorylates upon insulin binding, activating downstream signaling cascades including:

• PI3K/Akt pathway: Promotes neuronal survival, protein synthesis, and glycogen metabolism
• MAPK/ERK pathway: Regulates cell growth, differentiation, and synaptic plasticity
• IRS proteins: Key adaptors linking IR to downstream effectors

Synaptic Plasticity and Memory

Insulin signaling modulates synaptic plasticity—the cellular basis of learning and memory—through multiple mechanisms:

• LTP induction: Insulin facilitates [long-term potentiation](/mechanisms/long-term-potentiation) in hippocampal neurons
• AMPA receptor trafficking: Insulin regulates AMPA receptor insertion into synaptic membranes
• Dendritic spine morphology: Insulin influences spine density and morphology
• Neurotransmitter regulation: Modulates GABAergic and glutamatergic signaling

Insulin Resistance and Neurodegeneration

The Type 3 Diabetes Hypothesis

Epidemiological studies have revealed a strong association between type 2 diabetes mellitus (T2DM) and increased risk of [Alzheimer's disease](/diseases/alzheimers-disease), leading to the hypothesis that AD may represent a form of "type 3 diabetes" [3]. This hypothesis posits that brain insulin resistance contributes to:

Evidence from Studies

• Postmortem brain studies show reduced insulin receptor expression and signaling in AD patients [4]
• Cerebrospinal fluid insulin levels are decreased in AD patients
• Intranasal insulin administration has shown cognitive benefits in clinical trials
• Animal models of insulin resistance exhibit amyloid and tau pathology

Therapeutic Implications

Intranasal Insulin

Intranasal delivery of insulin bypasses the blood-brain barrier and has been investigated as a potential therapy for AD. Clinical trials have demonstrated:

• Improved memory and cognitive function in AD patients
• Modulation of amyloid metabolism
• Enhanced functional connectivity in memory networks

Insulin Sensitizers

Drugs that improve insulin sensitivity, such as thiazolidinediones (PPARγ agonists), have shown promise in preclinical models:

• Reduced amyloid pathology in mouse models
• Decreased neuroinflammation
• Improved neuronal survival

Lifestyle Interventions

Metabolic and lifestyle factors that improve insulin sensitivity may reduce neurodegeneration risk:

• Regular physical exercise
• Ketogenic diets
• Caloric restriction
• Adequate sleep

Summary

Insulin is a crucial hormone for both peripheral metabolism and brain function. In the brain, insulin acts as a neurotrophic factor regulating synaptic plasticity, memory, and neuronal survival. Insulin resistance—common in aging and type 2 diabetes—emerges as a significant contributor to [Alzheimer's disease](/diseases/alzheimers-disease) pathogenesis. Understanding the role of insulin signaling in neurodegeneration offers therapeutic avenues for disease modification in AD and related disorders.

See Also

• [INS Gene](/genes/ins)
• [Alzheimer's disease](/diseases/alzheimers-disease)

External Links

• [GeneCards: INS](https://www.genecards.org/cgi-bin/carddisp.pl?gene=INS)

References