You may have heard of Insulin before, especially if you know somebody who has Diabetes. Insulin is a hormone that helps the body use or store glucose in the bloodstream. People with Type II Diabetes have developed a resistance to Insulin and can suffer from chronic high blood sugar levels. An interesting connection to Alzheimer’s disease is that there is a link between defective insulin signaling and decreased insulin receptiveness in the brains of those with Alzheimer’s disease.
When Insulin binds to its receptor, two major signaling pathways are triggered, the PI3K and MAPK pathways. In patients with that have developed insulin resistance, the PI3K pathway is hindered while the MAPK pathway is left unhindered. The PI3K pathway is a critical pathway that plays an important role in food intake, liver glucose production, plasticity, learning and memory.
The PI3K pathway is critical for it has many benefits, one of the most pertinent, being its neuroprotective effects. The PI3K pathway inhibits glycogen synthase kinase (GSK3) activity and also inactivates the transcription activity of forkhead box protein O1 (FOXO1). This helps to decrease liver glucose production (through phosphorylation of FOXO1), to prevent the formation of Amyloid-Beta plaque buildups, and to prevent the hyperphosphprylation of tau proteins, the latter two known to be involved in Alzheimer’s disease.
As you can see from the paragraph above, there is a close and direct link between the PI3K pathway and both Alzheimer’s disease and Diabetes. By promoting the PI3K pathway, the inhibition of GSK3 could possibly provide therapeutic effects for patients suffering from both diseases. The use of insulin is commonplace for treatment of diabetes, but what is of interest to me is how it will be used for possible treatment in patients with Alzheimer’s disease. Furthermore, exploring alternate insulin related pathways to possibly treat Alzheimer’s disease would be interesting. Such treatment could include current treatment for Type II Diabetes. Understanding the link between insulin resistance and Alzheimer’s may bring us one step closer to curing this debilitating disease.
Information for this post taken from:
http://www.sciencedirect.com/science/article/pii/S1552526013029221