Insulin: impacting more than just diabetes

Those impacted by Alzheimer’s disease (AD) has reached an alarming number of 5 million individuals as of 2015 in the United States alone. AD has no cure, which is why the diagnosis can often be so hard on friends and family. Memory loss, general confusion, and difficulty concentrating characterize the disease, which can all be blamed on the formation of beta amyloid plaques and neurofibrillary tangles in the brain.
 
But wait, the Title mentioned diabetes, not Alzheimer’s disease. Where is this going?!
 
Type II diabetes is not categorized as a neurodegenerative disease like AD is. But Type II diabetes itself impacts 90-95% of those diagnosed with any form of diabetes. The disease is characterized with what is called “insulin resistance.” This phenomenon is where the body is unable to properly create enough insulin. Or enough insulin is being produced, but insulin in general is unable to bind to its insulin receptor.
 
But what in the world does Type II diabetes have to do with AD?
 
Calm down and let me tell you.
 
New research is discovering a similarity in the pathways of Type II diabetes and Alzheimer’s disease. The two major pathways have been labeled MAPK and PI3K.
Two of the major problems that differentiate AD from other neurodegenerative diseases are the formation of amyloid beta plaques and neurofibrillary tangles. These plaques and tangles can be traced back to a malfunction of insulin in the PI3K pathway.

Looking exclusively at the PI3K pathway of the cell, neurofibrillary tangles are formed when glycogen synthase kinase 3 beta (GSK3ß) is NOT inhibited. The inhibition of this particular kinase can be traced all the way back to the successful or unsuccessful binding of insulin (refer to yellow circle titled ligand below) to a specific type of receptor tyrosine kinase, in this case an insulin receptor (refer to blue prong-like image below). If insulin is successfully able to bind to its receptor, a series of excitatory or inhibitory signals occurs. As the picture below refers to, a series of excitatory signals must occur in order for GSK3ß to successfully be inhibited. Successful inhibition reduces the amount of protein (specifically tau) phosphorylation.

 
In a healthy neuron, tau proteins bind and support the microtubules found in the axon of a neuron. Unfortunately, in the case of those with Alzheimer’s disease, if the inhibitory signal is not received to the GSK3ß, the protein tau continues to phosphorylate, causing its normal function in binding and stabilizing microtubules to cease, dissociating the microtubule all together, leading to the neurofibrillary tangles (as can be seen by the image below).

 
Yes, I get it. This is a lot of information that is very easy to think has completely gone in over the head. Let me try and sum all of this up for you.
 
Take home message: Insulin is a hormone that plays a very important role in both diabetes and Alzheimer’s disease. Too much or too little insulin is never good. The unfortunate part of all of this is that no one really knows the exact amount of insulin needed in the body for everything to function properly. Insulin, when properly binding, has the ability to inhibit the formation of beta amyloid plaques and neurofibrillary tangles and promote neuronal growth within the brain, which can lead to improvements in cognition.
 
The question remains: Are those who suffer from Type II diabetes more prone to Alzheimer’s disease, as improper binding of insulin is categorized in both Type II diabetes and Alzheimer’s disease?
 
The discoveries researchers are finding that show how insulin plays a role in both AD and Type II diabetes will hopefully lead future researchers to something that doesn’t go over everyone’s head:
 
A cure.