Diabetes Leading to Alzheimer’s Disease.
KATP channels, like a radar system in our bodies, help regulate various bodily functions. This study expands on previous research suggesting that high blood sugar levels can influence the release of a protein called Aβ in brain cells, which may play a role in diseases like Alzheimer's. We have explained in the past that insulin resistance can lead to Alzheimer’s disease.
In their previous studies, they found that high blood sugar levels could lead to an increase in Aβ release. They delved deeper into understanding the role of a specific part of the KATP channel, called Kir6.2, in this process. Their experiments confirmed that mice with higher levels of Kir6.2 and high blood sugar released more Aβ. Also, blocking the KATP channel activity stopped the release of Aβ, further confirming the role of these channels.
They also conducted experiments using a drug called glibenclamide that influences the activity of KATP channels. It made cells more active, leading to more Aβ release. These results showed that KATP channels, especially the Kir6.2 part, can control how Aβ is released depending on the cell's activity level.
When they changed sugar levels either quickly (acute hyperglycemia) or over a longer time (chronic sugar consumption), they learned more about how KATP channels function in metabolism and their connection to Alzheimer's disease. Surprisingly, Aβ deposition (the building up of the protein) in mice didn't change under normal conditions but only when sugar levels were high.
This sparked curiosity as to why this was happening. One possibility they considered was that other channels might be compensating for the lack of Kir6.2 channels, but testing disproved this theory. Another theory considered was that Kir6.2 channels might be balancing the activity of other neurons to prevent overactivity. This will need more research to be confirmed.
Moreover, they found that these channels are not needed for sugar transport into the brain. They are mainly found in neurons and have a minimal presence in cells responsible for glucose uptake from blood to brain. Hence, their absence wouldn't affect energy availability.
The study also found an interesting connection between KATP channel activity and the production of a substance called lactate. Higher lactate levels may play a role in Aβ aggregation (the clumping together of proteins), which is a characteristic of Alzheimer's disease.
Furthermore, they found that long-term exposure to a high-sugar diet increased Aβ levels and plaque deposition in mice that had intact Kir6.2 channels. This shows a step-by-step process of how these channels might influence Alzheimer's disease progression when blood sugar levels are irregular.
Finally, the study provides a new perspective on why people with prediabetes or Type 2 diabetes might have a higher risk of developing Alzheimer's. High sugar intake can drive Aβ buildup, even without the presence of obesity or metabolic syndrome. This suggests that controlling KATP channels or changing diet to lower carbohydrate intake might help reduce the risk of Alzheimer's in people with diabetes or prediabetes.
We foresee a focus and an opportunity for drug companies to target this receptor to prevent the formation of these Alzheimer’s tangles. . . many years down the road, and at what financial cost to people? We could always just decrease the amount of sugar we bring into our bodies.
Jason & Rita
