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Alzheimer’s disease mechanism linked to diabetes

Rachel Soon
Medical Writer
06 Feb 2017
Sad elderly man contemplating

Similarities in insulin signaling mechanisms between the brains of Alzheimer’s disease patients and the pancreas of diabetic patients may point the way to improved treatment for the former, according to researchers.

Memantine, a drug already in use for Alzheimer's disease, is a known inhibitor of N-methyl-D-aspartate (NMDA) receptors that prevent excessive glutamate transmission in the brain. Researchers have now found that memantine also inhibits Kir6.2, an ATP-sensitive potassium channel, thus improving insulin signal dysfunction in the brain of mouse models. [Molecular Psychiatry 2016;doi:10.1038/mp.2016.187]

"In the pancreas, the Kir6.2 channel blockade increases insulin signaling, and insulin signaling decreases the blood glucose levels," says Dr. Shigeki Moriguchi, senior assistant professor at the Tohoku University Graduate School of Pharmaceutical Sciences. "In the brain, insulin signaling increases the acquisition of memory through CaM kinase II activation by Kir6.2 channel blockade."

In their experiment, Moriguchi’s team indicated that memantine treatment could improve impaired hippocampal long-term potentiation (LTP) and memory-related behaviors in the mice through Kir6.2 inhibition. They concluded that Alzheimer's disease could be described as a diabetic disorder of the brain.

"Since KATP channels Kir6.1 or Kir6.2 are critical components of sulfonylurea receptors (SURs) which is downstream insulin receptor signaling, the KATP channel inhibition by memantine mediates the anti-diabetic drug action in peripheral tissues," says Dr. Moriguchi. "And this leads to improved cognitive functions and improved memory retention among Alzheimer's patients."

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Most Read Articles
07 Oct 2019
In pancreatic cancer patients undergoing chemotherapy, the presence of diabetes mellitus is associated with reduced survival and larger tumour, as well as with increased risk of death after treatment, according to a meta-analysis.
Stephen Padilla, 07 Oct 2019
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