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Wednesday, March 14, 2012

The GUIDE: Diabetes and the Brain

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[Apologies for typing and phrasing problems.  I am suffering from very uncomfortable carpal tunnel syndrome this week.  This blog was dictated using Dragon Naturally Speaking.]

Today's blog is a bonus one that I hadn't intended to write, but recent family events have prompted me to talk about effects of diabetes on the brain. I'll start with a description of what exactly the disease we call diabetes consists of,then returned to the idea of what diabetes has to do with brain function. But I'll give you little hint, neurons and the support cells of the brain cannot make their own glucose from stored molecules; they are completely dependent on the blood supply for delivery of glucose.

Diabetes mellitus is the scientific name for diseases involving the production of insulin, which is necessary for transporting glucose into the cells of the body. There is another disease, diabetes insipidus, which is as many similar characteristics including excessive urination, but is essentially a kidney disease and does not involve insulin. Type I diabetes results when the pancreas cannot produce insulin. Type II diabetes results when the cells of the body don't respond to insulin. In both cases the body is unable to transport high concentrations of glucose from the blood into the cells that need it.

Insulin is produced in the pancreas by cells called Islets of Langerhans. From before birth these cells produce insulin whenever blood sugar (blood glucose) is elevated. Blood glucose increases after eating a meal, increases after exercise in order to replace the glucose used by the muscles, and it is increased during fever fighting disease. Most of the glucose in our body comes from the food we eat, and excess glucose is broken down then converted to longchain's of carbon known as fatty acids. Fatty acids together with triglycerides form the facts that are deposited in the adipose cells and forms the fat tissue of the body. When the body needs this extra energy, it breaks down fats and uses a process called gluconeogenesis to create glucose. Small amounts of glucose can also be stored as a complex molecule called glycogen, and most glycogen storage is in muscles that use it during exertion, and in the liver. Since alcohol contains a lot of glucose molecules one of the characteristics of advanced alcohol poisoning or alcoholism is extensive fat and glycogen deposits and the liver. Nutrients including glucose are absorbed into the blood stream from the food we eat, then passes through the liver for processing of the molecules and eventually ends up circulating in the blood, stored as glycogen in liver and muscles, or stored as fat in the liver and adipose tissue.

Glucose as a molecule however, it's too big to pass across the membrane into the cells of the body. A specialized transporter molecule latches onto the glucose and transported into cells. This transporter molecule requires insulin in order to activate, and if there is not enough insulin, or if the transporter and cells becoming sensitive to insulin, then the glucose builds up in the blood. Too much glucose in the blood means (A) that glucose is not getting inside the cells that need it, (B) that the glucose will remain in the blood until it is removed by other means. Usually this means that the kidneys have to filter the glucose out of the blood and into the urine, causing damage to the filtering cells of the kidney and showing up in urine tests. Too much glucose in the blood has another effect similar to too much salt in water, it increases the "osmotic pressure" of the blood and causes water to be drawn out of cells to dilute the high glucose concentration of the blood.

And thus we get to the effects of diabetes in the brain: Glucose is necessary for the function of brain cells, which fortunately are not as dependent on insulin for the uptake of glucose.  While not all of the effects of too much or too little insulin in the brain are known, too much glucose in the blood "dehydrates" brain cells via osmotic effects. A person who enters a diabetic coma, from too much glucose and too little insulin, is essentially suffering from a severe case of dehydration of the brain cells. In fact, dehydration in general can be associated with disruptions in the insulin and glucose balance in the blood.

Other factors involved come from the fact that without insulin, the cells of the body send signals for more glucose.  The liver starts breaking down fats (yielding a lot of methyl and ethyl ketone byproducts) and cells produce a lot of lactic acid from alternate energy molecules.  The resulting "diabetic ketoacidosis" can also be associated with weakness and coma since the acid and ketone molecules disrupt normal neurotransmitter and glucose uptake mechanisms int he brain.  So uncontrolled diabetes can cause the "double whammy" effect on the brain both from osmotic and metabolic causes.

There is another role for insulin in the brain, besides the glucose transporter (which, as stated above, is different in the brain and does not require insulin).  Many recent studies have shown that there are insulin receptors on neurons and glial (support) cells in brain, and that some specialized cells might produce very small amounts of insulin.  Insulin does not easily cross the blood brain barrier, but may be actively transported and can reach the brain through the nasal mucosa.  Insulin in the brain appears to improve memory, alertness, attention, and it acts as a neuroprotectant in case of brain injury. 

There are many myths about diabetes - the first being that "juvenile diabetes" (Type I, insulin insufficiency) occurs only in the young, and you're either born with it or not.  The second is that adult-onset diabetes (Type II, insulin insensitivity) is caused by overeating.  The truth is that either disease can occur at just about any age, and comes not from diet, but from the body's metabolism.  Getting fat doesn't cause Type II diabetes, but it does likely indicate that the body is already insensitive to insulin (thus carbohydrates in the diet are turned into fat and not metabolized).  A given person can also convert from Type II to Type I very suddenly:  a long period of uncontrolled Type II diabetes requires increased insulin production by the pancreas, and the over-stimulation can result in an abrupt "crash" if those same cells become diseased or inactive.  There is a large genetic component, but we still don't really know what causes islet cells in the pancreas to die or not produce insulin, but there are some intriguing gene and stem cell therapies that should start becoming available in the next 5 years.

So, contrary to some popular opinion that Type II diabetes is a gimmick to sell more pharmaceuticals, it is a real problem, with real consequences both to the body and to the brain.

3 comments:

  1. Thank you for this information.

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  2. The brain uses insulin? I had no idea! Thank you for taking the time with this series - not only am I learning something new, but it hits close to home, too!

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  3. Yup, the brain sure does use insulin. In fact, insulin may be assist in alertness and memory and could eventually be part of a treatment for Alzheimer's Disease. There is so much we still have to learn.

    Actually, the thanks is mine. I appreciate my readers and thte encouragement to continue!

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