Brain insulin resistance is a complex phenomenon that impairs insulin signaling in the central nervous system (CNS), with profound impacts on cognition, mood, and metabolic regulation. It is strongly associated with conditions such as type 2 diabetes, obesity, Alzheimer’s disease, and mood disorders. This article comprehensively describes the symptoms and mechanisms underlying this condition, including the neurotransmitters and brain subregions affected.
Symptoms of Brain Insulin Resistance
1. Cognitive Symptoms
• Memory deficits:
• Mainly in the hippocampus, a region crucial for memory formation and retention, due to dysfunction in insulin signaling that impairs synaptic plasticity.
• Learning difficulties:
• Reduced activation of pathways such as PI3K/Akt compromises molecular mechanisms involved in learning.
• Impaired executive functions:
• Difficulty planning, making decisions, and solving problems due to dysfunction in the prefrontal cortex.
• Disorientation and confusion:
• Commonly associated with the progression of dementia and neurodegenerative diseases such as Alzheimer’s.
2. Emotional and Mood Symptoms
• Depression:
• Alteration in the mesolimbic dopaminergic circuit, particularly in the nucleus accumbens, leading to anhedonia (inability to feel pleasure).
• Anxiety:
• Increased monoamine oxidases (MAO) that alter the metabolism of serotonin and dopamine, exacerbating anxiety symptoms.
• Apathy and lack of motivation:
• Results from reduced dopaminergic signaling in regions such as the striatum.
3. Metabolic and Neurological Symptoms
• Chronic fatigue:
• Insulin resistance in the brain reduces glucose metabolism, leading to low energy levels in the central nervous system.
• Frequent headaches:
• Resulting from energy dysfunction and increased oxidative stress.
• Changes in appetite:
• Insulin regulates eating behavior via the hypothalamus. Its dysfunction can result in binge eating or anorexia.
• Muscle pain and cramps:
• Related to the impact on the motor cortex, which suffers from insufficient glucose availability.
4. Symptoms Related to Alzheimer’s Disease
• Accelerated progression of dementia:
• The accumulation of beta-amyloid and hyperphosphorylation of tau, markers of Alzheimer’s, are directly linked to insulin dysfunction in the CNS.
• Changes in sleep:
• Insulin resistance affects areas such as the suprachiasmatic nucleus, impairing the sleep-wake cycles.
Reasons and Underlying Mechanisms
1. Regulation of Neurotransmitters
• Dopamine:
• Insulin modulates the release and reuptake of dopamine in areas such as the striatum and prefrontal cortex. In insulin resistance, there is a significant reduction in dopaminergic activity, contributing to symptoms of apathy, anhedonia, and cognitive dysfunction.
• Serotonin:
• Brain insulin dysfunction leads to increased monoamine oxidase (MAO) activity, resulting in reduced serotonin availability and worsening symptoms of anxiety and depression.
• Glutamate:
• Insulin regulates the release of glutamate, which is essential for synaptic plasticity. Its dysfunction causes excessive neural excitation, causing neuronal damage.
2. Affected Brain Subregions
• Hippocampus:
• Mainly affected due to reduced glucose uptake and insulin signaling, impairing memory and learning functions.
• Prefrontal cortex:
• Impaired executive function, leading to difficulties in planning and decision-making.
• Nucleus accumbens:
• Alterations in reward circuits cause loss of motivation and pleasure.
• Hypothalamus:
• Dysfunctions in appetite regulation and metabolic control.
3. Oxidative Stress and Inflammation
• Oxidative stress and chronic inflammation are triggers for brain insulin dysfunction. Increased inflammatory cytokines, such as TNF-α, activate insulin inhibitory pathways, such as JNK and mTOR, further impairing intracellular signaling.
4. Energy Dysfunction
• Insulin regulates glucose uptake in the brain. Its resistance reduces the energy available for neuronal functions, aggravating fatigue and cognitive impairment.
Conclusion
Brain insulin resistance is a multifaceted condition that affects the individual’s metabolic, cognitive, and emotional functioning. Its clinical manifestations result from alterations in neurotransmitters and critical brain areas, in addition to inflammatory processes and energy dysfunctions. Recognizing these symptoms and understanding the underlying mechanisms is essential for early interventions and targeted treatments.
Dr. Fabiano de Abreu Agrela Rodrigues MRSB holds a post-PhD in Neuroscience and is an elected member of Sigma Xi – The Scientific Research Honor Society (more than 200 members of Sigma Xi have received the Nobel Prize), as well as being a member of the Society for Neuroscience in the United States, the Royal Society of Biology and The Royal Society of Medicine in the United Kingdom, the European Society of Human Genetics in Vienna, Austria, and the APA – American Philosophical Association in the United States. He holds a Master’s degree in Psychology and a Bachelor’s degree in History and Biology. He is also a Technologist in Anthropology and Philosophy, with several national and international degrees in Neuroscience and Neuropsychology. Dr. Fabiano is a member of prestigious high IQ societies, including Mensa International, Intertel, ISPE High IQ Society, Triple Nine Society, ISI-Society, and HELLIQ Society High IQ. He is the author of more than 300 scientific studies and 30 books. He is currently a visiting professor at PUCRS in Brazil, UNIFRANZ in Bolivia and Santander in Mexico. He also serves as Director of CPAH – Centro de Pesquisa e Análises Heráclito and is the creator of the GIP project, which estimates IQ through the analysis of genetic intelligence. Dr. Fabiano is also a registered journalist, having his name included in the book of records for achieving four records, one of which is for being the greatest creator of characters in the history of the press.