Cobbers on the Brain

Insulin

Insulin is a peptide hormone with numerous functions in the body, the most common of which is to control glucose levels. Insulin acts differently in the pancreas, liver, bones, and so on than it does in the brain. Insulin regulates neuron growth, survival, differentiation, and communication in the brain. So, what happens when insulin is not properly regulated?

Insulin resistance

This is a condition in which the body and brain are unable to use glucose as an energy source effectively. The ability to be insulin sensitive is lost, and as a result, glucose absorption by brain cells is compromised. Insulin regulates brain metabolism and overworked insulin receptors cause brain cells to die. Chronic oversupply of glucose to brain cells causes the cells to overwork in order to metabolize the excess fuel, eventually giving up and committing suicide via a process known as apoptosis.  

This has an effect on neuro communication in the brain because glucose is what the cells require to function properly. At this point, the brain is essentially starving. There is an abundance of glucose but no way to use it. 

 High carb content diets, like the typical American diet promote chronic and prolonged blood sugar spikes. This prolonged glucose overdose starves the brain and later  manifests itself as cognitive impairment. Cognitive ability is directly proportional to energy supply to the brain.

Diabetes

It is critical to distinguish between type I and type ii diabetes. We lack the ability to produce insulin in type I diabetes, so glucose levels in our bodies are high. In type II diabetes, however, insulin is present, but it is excessive, and our cells become resistant to it, raising glucose levels to dangerously high levels. When we think of diabetes, we usually think of the heart, kidneys, and pancreas as the most affected organs. But what about the brain? 

Diabetes accelerates brain aging, which, as we know, causes neurodegenerative diseases such as Alzheimer’s. Blood flow to the brain is reduced in diabetic patients, causing neuron damage. These neurodegenerative changes occur at a much earlier stage. Diabetes also impairs byproduct metabolism in patients, resulting in the buildup of undesirable substances such as amyloid plaques and neurofibrillary tangles found in Alzheimer’s disease.

In diabetes, people have smaller brain volume of the frontal and temporal lobes due to brain atrophy triggered by excessive cell apoptosis.

Inflammation and Alzheimer’s Disease

When most people hear the words Alzheimer’s disease, they envision plaques and tangles. We know that amyloid plaques and neurofibrillary tangles are major indicators of neurodegenerative disease, most notably Alzheimer’s disease.

Plaques cause one of three problems in the brain:

• Disruption of neuron communication by acting a physical barriers in synapses
• Trigger inflammation through the intervention of the immune system
• Increased risk of hemorrhage in blood vessels through amyloid angiopathy

Tangles form when plaques accumulate outside of neurons. Tangles cause significant disruption in the cell’s transport system, the microtubules.

Tangles, combined with plaque buildup, eventually cause the cells to die via apoptosis. This explains why reduced brain atrophy, a condition caused by too much cell death in the brain, is a major symptom of Alzheimer’s disease.

If this blog is to be of any use to you, I want you to be able to link insulin to the formation of plaques and tangles, and, in the larger picture, Alzheimer’s disease.

When you hear insulin typically you think of blood sugar, the pancreas, or diabetes. Did you know it is in your brain as well? Well, if you didn’t no worries, until recently the brain was classified as an organ without it or just insensitive to insulin. Before we get into the logistics. Let’s review what insulin is exactly.

Insulin, when created in the pancreas is a hormone the allows glucose (aka sugar) to enter your blood stream. While in the brain it actually functions as a neuromodulator that helps neurons exist. According to a review, it is involved in neuronal survival, energy production, gene expression, and synaptic plasticity. As well as the breakdown of glucose as well. Metabolism or breakdown of glucose in the brain has been linked to have effect on how your neurons are able to learn and a persons’ memory.

A study has also showed that in mice neurons contain mRNA of preproinsulin. Which is insulin but in its’ “pre-hormone state”. It was found in all parts of the neuron including synapses. This leads to the synthesis of insulin. Insulin can also enter the brain from systems outside of the CNS. It enters through the BBB (blood brain barrier) by beta pancreatic cells.

So how does all this pertain to Alzheimer’s disease? (AD) Well, the by mistakes in the insulin pathways in the brain. Or a more common term, insulin resistance. Insulin receptors which control the breakdown of glucose in the brain. In turn can regulate of the overall health of neurons. Well, if the transmission of insulin gets wonky or in scientifical terms things like beta amyloid competition. Insulin cannot bind as well, which can lead to neuronal death. Therefore, insulin resistance can increase the pathology of AD.

Not only does insulin play a role in cognitive functions. Studies have also shown that it plays a role in anxiety and depression in the brain. Neuronal-specific insulin receptor knockout (NIRKO) has shown to increase anxiety and depression like symptoms in mice. Research has also shown that insulin can alter body weight and appetite. It can both increase and decrease appetite, which one? Well, it depends on how the insulin got to the brain.  Shockingly it increases appetite when insulin enters the brain peripherally. Synthesized insulin or the insulin made in the brain is what can cause a decrease in appetite and lowers body weight. Below is a little figure that I find helpful to keep track of how insulin plays a role in all parts of our bodies. And how in each part in changes different things for us.

Being that research about insulin in the brain is all new, the possibilities of new findings can lead to remarkable actions we may be able to take to monitor our own health. Insulin in the brain has already been linked to having effects memory, neurological diseases, mental health, and our physical health like appetite and weight. Who knows maybe one day insulin will be something everyone will be familiar with, not just those who have to monitor blood sugar levels. It will be something everyone will want to monitor for themselves to live a long and better quality life.

Alzheimer’s disease and broader dementia are a growing epidemic challenging care for global ageing populations. Characterised as a neurodegenerative disease, Alzheimers involves the degeneration of the brain and a subsequent loss of cognitive function. Memory loss, confusion, and delusion all plague patients with Alzeihmers, and so too, the family and caregivers who care for these individuals. As this disease becomes more prevalent amongst our future ageing population, intriguing research is coming forward on the causes of Alzheimer’s and even some of the ways to prevent it. A review by Ansab Akhtar and Sangeeta Pilkhwal Saw out of Punjab University in Chandigarh, India is presenting some useful insight on the effects of insulin to the brain. 

In order to understand this, however, we must first assess the two largest factors that contribute to the neurodegeneration in Alzheimer’s disease. The first is amyloid-ꞵ plaques. ꞵ-amyloid is a small protein that can misfold and connect with other ꞵ-amyloids to form a plaque-like formation outside of a cell. When this plaque forms, it inhibits the binding of insulin to its receptors in the brain. The second contributor to Alzeimhers important in understanding the effects of insulin are neurofibrillary tangles or NFTs. NFTs arise when Tau proteins become hyperphosphorylated leading to tangle formation in microtubule networks which leads to their collapse. In other words, look at Tau protein as a Jenga block at the very bottom of a tower that resembles the framework of a cell, otherwise known as microtubules. When this block is removed, the microtubule tower falls and so does the cell that it provided a framework for. NFTs are much like the fall of a Jenga tower. 

Insulin is crucial to the action of both amyloid-ꞵ and NFTs. Insulin is responsible for regulating blood sugar throughout the body but it plays a valuable role in protecting the neurons in the brain. The review by Akhtar and Saw provides insight into how the brain developing resistance to insulin is related to the formation of amyloid-ꞵ plaques and NFTs. The first figure placed in the review shows the various ways the insulin signalling pathway can be affected. Many of the molecules inside the cell can contribute to NFT formation internally whilst also allowing amyloid-ꞵ to be produced which can stop insulin signalling all together at its receptor. When there is dysfunction of this insulin pathway, the neurons do not function optimally and often undergo apoptosis, which is programmed cell death. 

Understanding insulin resistance is valuable in understanding Alzheimers and treating it in our future. Processed food products are used by societies across the globe to ensure cheap and abundant food. This abundance, however, has led to metabolic syndrome and an increase in insulin resistant diabetes in our communities. Being one of the largest contributors to these problems, changing our diets should be a starting point. Whole, unprocessed foods take more metabolic effort to digest and minimise the blood sugar spikes we see from processed counterparts. Much like how they slow down digestion, these whole foods also slow down our day to day lives. Taking more time to focus on our diet also allows us to make greater effort towards our physical activity. A healthier society may see less insulin resistance which may be one of the first steps we can make to stopping Alzheimer’s disease in its tracks. 

Ansab Akhtar and Sangeeta Pilkhwal Saw, “Insulin signaling pathway and related molecules: Role in neurodegeneration T and Alzheimer’s disease” Neurochemistry International 135, (2020)