It is a little-known fact that nerve cells (or neurons as they are called) share more similarities with the cells in the pancreas that make insulin (the pancreatic islet cells called beta cells) than any other cell type in the body.  As it turns out, this is no small  coincidence.  For one thing, they both synthesize and secrete compounds that send signals to other cells.  In the brain these compounds perform like hormones that act over short distances and are called neurotransmitters.  Examples are serotonin (the feel-good compound), dopamine (the focusing compound), norepinephrine (the alerting compound) and many others.  In the pancreas, insulin (the blood-sugar controlling hormone) is synthesized, stored and secreted into the blood when called upon to control blood sugar levels.  Another recent discovery is that in the brain there are receptors (unique docking proteins located in the membranes encapsulating nerve cells) that bind and are activated by insulin.  Even more recently it was discovered that certain neurons in the brain are actually able to synthesize and secrete insulin, which appears to be identical to the insulin produced in the pancreas.  That this occurs is not controversial.  However, what is uncertain is what exactly insulin does in the brain. 

Sometimes it is easier to determine what biological role a compound plays when investigators analyze the circumstances when it is absent.  A rodent study addressed this very issue for insulin.  This experiment suggested that Alzheimer's disease may be caused by a deficiency in brain insulin.  Suzanne de la Monte and colleagues at Brown University in Providence, Rhode Island, had previously shown that insulin was produced in the brain.  She believed it was vital for the survival of neurons.  When they analyzed the brains of post-mortem Alzheimer's patients, they identified reduced concentrations of insulin in their brains.  Based upon these observations, they created a rodent model that mimicked the human condition by causing a fall of insulin levels in the brains of these rodents.   They subsequently documented the death of insulin producing neurons and the delayed development of dementia as determined by performance on the Morris Water Maze test that was administered to the rodents.  Death and degeneration of neurons were not the only findings they observed.  There were also increased concentrations of phosphorylated tau proteins in the brain.  In Alzheimer patients the level of phosphorylated tau proteins parallels the cognitive deterioration.  An enzyme that contributes to the density of phosphorylated tau proteins is GSK (Glycogen Synthase Kinase).  It is under the control of insulin.  With low insulin levels its activity increases and the number of phosphorylated tau proteins increases.  These striking findings suggest that insulin deficiency in the brain may trigger Alzheimer's disease.  The nexus between neurodegeneration and insulin deficiency raises the possibility that Alzheimer's disease is a brain-specific neuroendocrine disorder.  For this reason de la Monte has suggested an alternative name for this disorder-Type III diabetes.  Type I and Type II diabetes result when the body can't produce enough insulin or is resistant to its actions.  She describes Type III diabetes as a brain-specific form incorporating features of both Type I and Type II diabetes where insulin secreting neurons die and other neurons become resistant to the actions of insulin.

That this novel reformulation of Alzheimer's disease is not so far fetched is suggested by the rodent experiments already mentioned as well as human studies documenting the beneficial impact on mental acuity of pharmaceuticals designed to enhance insulin sensitivity  in patients with Alzheimer's disease.  What is even more remarkable is that this suggests that other non-pharmaceutical interventions able to improve insulin sensitivity might well be able to lower the risk of developing Alzheimer's.  Such interventions include  common lifestyle choices entirely under our control such as diet, exercise, smoking, excessive drinking and engaging in a mentally challenging lifestyle. 

It seems intuitive that if the brain burns glucose, that more would be better for brain health and functioning.  In the long-term this is clearly not the case because high glucose levels are a potent factor contributing to brain shrinkage, or atrophy, and the development of insulin resistance-a condition that predisposes to low brain insulin levels with the possible complications we have previously discussed.   What is clear is that ongoing high levels of mental acuity rely on a stable, moderate supply of glucose.  Not too much and not too little.  What determines this is almost entirely under our control and something that will be discussed in the next article.   This is important because disorders such as insulin resistance, pre-diabetes and frank diabetes increase the likelihood of memory and mental problems such as Alzheimer's disease two to four fold.