Metabolic Disorders

Zombie Research Institute

Metabolic Disorders

Obesity

The orexin system in fundamentally involved in regulating feeding and digestive activities including blood glucose control.

Orexin receptors are found in human adipose tissue which suggests a role for orexins in adipose tissue metabolism and proliferation.
Low circulating orexin-A concentrations have been shown to be associated significantly with severe obesity (overproduction of white fat).
It has also been shown that orexin stimulates the production of brown fat. Orexin deficient animals produce less brown fat (which burns energy) and have lower basal metabolisms. This results in individuals who actually eat less but weigh more than the normal population.

I believe the mechanism causing these effects is altered insulin reponse due to orexin deficiency.

The glucose sensing properties of orexin cells allow it to regulate energy resources around the body. And one of the most important ways it does this is by affecting the release of insulin from the pancreas.

Insulin is a hormone that is produced by the beta cells in the pancreas. Insulin is released into the blood stream and travels throughout the body where it promotes the uptake of carbohydrates by cells and consequently lowers blood glucose levels.

Here's how it works: Orexin regulates the release of insulin from the pancreatic beta cells- it suppresses insulin production.

-So when your blood sugar is low, your orexin is high and you make less insulin.

-After you eat, your blood sugar rises, orexin levels drop in the pancreas, and then the beta cells start producing and releasing insulin to metabolize the glucose.

I've simplified quite a bit. Pancreatic cells sense glucose too, and will produce insulin on their own, but orexin amplifies or suppresses the activity.

It gets complicated, there are a lot of other hormones and organs that participate in blood sugar regulation. I will limit myself to how orexin dysfunction could affect the system.

Orexin suppresses insulin production.

So impaired orexin function can be expected to result in excess insulin- Hyperinsulinemia.

Hyperinsulinemia leads to Obesity.

If you are Hyperinsulinemic and eat high carbohydrate meals, you will become hypoglycemic- the excess insulin converts most of the food to fat and starves your body and brain of glucose. Not surprisingly- low blood sugar also causes a desperate craving for food. If you continue to eat a high carb diet, you just compound the process. The more carbs you eat, the fatter and hungrier you get. (Protein and fat do not stimulate the pancreas to produce insulin.)

Insulin also inhibits use of fat as an energy source. So even if you lower your caloric intake, you won't lose weight.

Women are more prone to these metabolic effects because estrogen also acts directly on beta-cells and increases insulin production.

Hyperinsulinemia also leads to Insulin Resistance.

Insulin Resistance is a condition in which the cells of the body become resistant to the effects of insulin. As a result, higher levels of insulin are needed in order for insulin to have its effects. Insulin itself can lead to insulin resistance; every time a cell is exposed to insulin, the production of glucose receptors on the cell's membrane is decreased. This leads to a greater need for insulin, which again leads to fewer glucose receptors.

Impaired insulin function in the brain is highly correlated with cognitive and memory problems.

If your orexin cells are damaged-

Your ability to metabolize carbohydrates is drastically reduced.

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Alcoholism

Alcohol is an alternate form of sugar, and alcoholism is an alternate carbohydrate metabolism. Although alcoholism is a problem in modern society, historically the ability to consume alcohol has been an advantage for humans. Many water borne diseases cannot survive in an alcohol solution, so it was often safer for consumption.

Likewise - Gliadin dissolves in alcohol. Drinking may actually reduce the immune response. It also takes over your liver and halts glycogen production.

Alcohol metabolism is strongly dependent on orexin.

In rats, injection of orexin into the appropriate location in the hypothalamus significantly increased ethanol intake instead of food intake, and the destruction of orexin cells inhibits alcohol seeking.
Ethanol consumption also increases with expression of orexin receptors.
Orexin also significantly inhibits the severity of stomach lining damage by ethanol.

As an alternate carbohydrate, the metabolic pathway is a bit different and also causes Hyperinsulinemia.

In the pancreas, ethanol acutely stimulates islet blood flow, amplifies insulin secretion, and induces hypoglycemia.
Chronic excessive alcohol consumption can significantly disturb the hypothalamic control of glucose metabolism. Abstinent alcoholics exhibit an exaggerated stress response to glucose challenge.

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This mechanism explains why we "fall off the wagon" and go on binges.

One good dose of sugar or alcohol and our entire system gets out of balance.

There is also this other phenomenon that results in unexpected symptoms:

The body's responses for the present meal are based on the last meal. You will create enough insulin and antibodies to cover the last meal whether they are appropriate for this one or not. Sometimes it's too much, sometimes not enough.

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So, I hope you get the message- we are prone to Hyperinsulinemia. We make too much insulin. And too much fat.

And that causes Hypoglycemia- Low Blood Sugar

We get fat on the outside while we starve on the inside.

Extreme hypoglycemia has a few other symptoms you may be familiar with-

Syncope-loss of conciousness
Hypotonia- loss of muscle tone

Many of the effects of narcolepsy not only cause, but are aggravated by rapid blood sugar fluctuations.

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