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Making Sense of the Relationship between Diabetes and Alzheimer’s Disease
Serenoa
Posted: Friday, April 15, 2016 4:26 AM
Joined: 4/24/2012
Posts: 484


Abstract

Numerous studies have documented a strong association between diabetes and Alzheimer’s disease (AD). The nature of the relationship, however, has remained a puzzle, in part because of seemingly incongruent findings. For example, some studies have concluded that insulin deficiency is primarily at fault, suggesting that intranasal insulin or inhibiting the insulin-degrading enzyme (IDE) could be beneficial. Other research has concluded that hyperinsulinemia is to blame, which implies that intranasal insulin or the inhibition of IDE would exacerbate the disease. Such antithetical conclusions pose a serious obstacle to making progress on treatments. However, careful integration of multiple strands of research, with attention to the methods used in different studies, makes it possible to disentangle the research on AD. This integration suggests that there is an important relationship between insulin, IDE, and AD that yields multiple pathways to AD depending on the where deficiency or excess in the cycle occurs. I review evidence for each of these pathways here. The results suggest that avoiding excess insulin, and supporting robust IDE levels, could be important ways of preventing and lessening the impact of AD.

http://content.iospress.com/articles/journal-of-alzheimers-disease/jad150980


Serenoa
Posted: Friday, April 15, 2016 4:38 AM
Joined: 4/24/2012
Posts: 484


Dr. Melissa A. Schilling has brilliantly put the evidence together that links insulin to Alzheimer's. In the above article she has recognized and described multiple ways in which dysfunctional insulin can result in disease. This is truly empowering. THIS IS PROGRESS!
Lane Simonian
Posted: Friday, April 15, 2016 11:42 AM
Joined: 12/12/2011
Posts: 4986


The relationship between insulin and Alzheimer's disease is quite important.  Too little insulin and too much glucose reaches the brain.  The glucose in the brain increases levels of myo-inositol and may overactivate platelet derived growth factor which leads to the formation of peroxynitrite.

http://diabetes.diabetesjournals.org/content/51/1/198.long

Too much insulin and the insulin receptor is over-activated leading to oxidation and nitration (it is the nitration of the insulin receptor substrate that likely causes type 2 diabetes).

http://www.ncbi.nlm.nih.gov/pubmed/15240096

Too little or too much insulin increases the risk of Alzheimer's disease for someone with diabetes.

Nitrostative stress may also reduce activity of the insulin-degrading enzyme but this is only significant if amyloid plaques play some role in Alzheimer's disease.

http://www.sciencedirect.com/science/article/pii/S0006295208008940

This chart is for vascular endothelial growth factor but it is applicable for any growth factor and growth factor receptors such as insulin receptors.

http://d1dvw62tmnyoft.cloudfront.net/content/joces/118/1/243/F7.large.jpg

In cancer, peroxynitrite activates cell growth pathways; in Alzheimer's disease it leads to cell death.


Serenoa
Posted: Tuesday, April 19, 2016 5:37 AM
Joined: 4/24/2012
Posts: 484


Berberine reduces insulin resistance through protein kinase C–dependent up-regulation of insulin receptor expression

http://www.sciencedirect.com/science/article/pii/S0026049508003272

Berberine, a Natural Plant Product, Activates AMP-Activated Protein Kinase

http://diabetes.diabetesjournals.org/content/55/8/2256.full


Lane Simonian
Posted: Tuesday, April 19, 2016 9:22 AM
Joined: 12/12/2011
Posts: 4986


This is a good find, Serenoa.  Berberine and other similar compounds are also good antioxidants which may help in the treatment of Alzheimer's disease.

Along with use for diabetes, dyslipidemias, and cardiovascular conditions …

Berberine is a Multipotent 
Anti-Alzheimer’s Weapon

http://www.life-enhancement.com/magazine/article/2484-berberine-is-a-multipotent-anti-alzheimers-weapon

Anti-Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids.

http://www.ncbi.nlm.nih.gov/pubmed/19652386


remembering
Posted: Friday, April 29, 2016 9:40 PM
Joined: 4/29/2016
Posts: 12


There has been some excitement about this one.

GLP-1 is a different take on the connection between diabetes and Alzheimer's.

Liraglutide is already a multi-billion dollar drug.   

http://www.express.co.uk/life-style/health/665115/Alzheimer-dementia-cure-drug-stop-disease