Insulin Resistance in the brain

Introduction

Over time, if you’re developing insulin resistance of the body, you’re also developing insulin resistance of the brain. Depending on the individual, this process of developing insulin resistance can focus primarily in the body or in the brain. Some people with insulin resistance will develop Alzheimer’s Disease, some heart disease, some Type 2 diabetes, some Cancer, some Polycystic Ovarian syndrome, etc. Why insulin resistance manifests in different ways is unclear, but it likely depends on depends on an individual’s genetics, lifestyle, environment, and other factors.

Nevertheless, there is a clear connection between insulin resistance and Alzheimer’s, so much so that in 2008 the term Type 3 Diabetes was coined as another way of referring to Alzheimer’s Disease. Alzheimer's Disease Is Type 3 Diabetes–Evidence Reviewed (Suzanne M. de la Monte, Jack R. Wands, 2008) Since 2008, there has been additional research, strengthening this link between Alzheimer’s disease (AD) and insulin resistance.

Type 2 diabetes is just one possible end result of insulin resistance. To be clear, while there is a strong relationship, one can develop Type 2 diabetes and never get Alzheimer’s. Conversely, one can have Alzheimer’s and not diabetes. One thing is clear, however, insulin resistance in the brain occurs in Alzheimer’s patients, regardless of if there is insulin resistance elsewhere in the body.

Insulin in a healthy body

Let’s review how insulin works in a normal, healthy body:

1. Food, particularly sugar and starches are broken down into blood glucose (see Blood Sugar).
2. The body prefers to keep glucose in the blood regulated to a near constant level (metabolic homeostasis), which is insulin’s function.
3. When blood glucose rises after a meal, the pancreas releases insulin to escort the glucose out of the bloodstream into cells where it’s needed. Insulin does this by binding to receptors on the surfaces of the body’s cells. The insulin is the “key” that fits in to the receptor to “unlock” the cell and let glucose in where it is needed.

Insulin resistance in the body

If a person eats a sugary/carby meal, the body will be flooded with glucose, more than it needs. The body pumps out lots of insulin to handle all this glucose, storing it (in the form of fat), in order to get the blood sugar levels back to normal.

Over time, with lots of sugary/carby meals and snacks, this process of excess insulin production causes damage to the body: the receptors become desensitized, the insulin receptors become numb to insulin. The insulin receptors also downregulate, I other words they become fewer in number. Fat is supposed to be stored in fat cells, called adipocytes, but in most people, this is a finite capacity. When the fat cells have become overfilled they can’t get enough oxygen and they become inflamed. When there’s no more room in the fat cells, the body then looks for other places to store fat, including where fat was never meant to go: the abdominal cavity (visceral fat), other organs (liver, pancreas, kidneys), and muscle. This ectopic fat (fat stored in areas besides fat cells) interferes with cellular functions and results in organ dysfunction, Like a splinter, ectopic fat is constantly annoying/stressing the body.

A condition commonly associated with persistent high insulin is Non-alcoholic Fatty Liver disease (NAFLD). A fatty liver is insulin resistant, so it’s not regulated by insulin appropriately, it keeps pumping out glucose (gluconeogenesis) even though the body doesn’t need glucose, thus exacerbating the problem. But when the pancreas is overtaxed but able to pump out enough insulin to maintain a relatively even and low level of glucose, that’s insulin resistance in the body (simplified). Insulin resistance develops over years. Without intervention, insulin resistance ultimately becomes Type 2 Diabetes. With Type 2 Diabetes, insulin no longer works well in the body and blood sugar levels stay high. A blood sugar test alone cannot determine if a person is insulin resistant, see Blood Sugar

Insulin resistance in the brain

Insulin resistance in the is different than insulin resistance in the body.

The Blood Brain Barrier Source: https://www.christopherreeve.org/blog/research-news/blood-brain-barrier-the-spinal-cord

In the body, glucose is escorted into cells through transporters called Glucose Transporter 4 (GLUT-4), these are regulated by insulin. But in the brain, blood vessels are surrounded by the Blood Brain Barrier (BBB). The Blood Brain Barrier adds a layer of protection for the precious brain. The endothelial cells of the BBB fit together tightly (tight junctions) so substances such as disease-causing pathogens and toxins cannot pass out of the bloodstream into the brain. But the brain doesn’t want to impair glucose from entering. Unlike in the body, on the blood brain barrier, there are what’s called Glucose transporter 1 (GLUT-1) receptors, they let glucose into the brain without being regulated by insulin.

The brain wants unimpaired glucose passage is because the brain needs fuel and lots of it. The brain uses more energy than any other human organ. It constitutes only 3% of the body's mass, but uses up 30% of the body's energy and it needs energy 24 hours a day.