Scientists believe that problems with how insulin works in the brain—especially in a part called the hippocampus—is linked to memory and thinking problems seen in conditions like Alzheimer’s disease. In earlier studies with rats, researchers found that when insulin didn’t work properly in the hippocampus, the rats had trouble learning and remembering things. Their brains also showed changes in structure and behavior, like signs of sadness and anxiety. The researchers also noticed changes in certain brain chemicals and proteins that help brain cells communicate, especially ones related to a system called the glutamatergic system, which is important for memory and learning.  This represented an important extension to prior research, which focused on the role of acetylcholine—another neurotransmitter implicated in Alzheimer's disease.

To learn more, the scientists studied how insulin problems in the hippocampus affect glutamate, a key brain chemical. They looked at how much glutamate was in the brain and how certain proteins involved in glutamate signaling were working. They also tested whether giving insulin through the nose could help. They found that rats with insulin problems had lower levels of glutamate and a drop in a protein called vGluT2. However, when these rats were given a high dose of insulin through the nose, their brains released more glutamate. This suggests that insulin problems can hurt brain communication, but giving insulin in the right way might help fix it.

Learn more about the study:

Hippocampal-Specific Insulin Resistance Elicits Synaptic Effects on Glutamate Neurotransmission

Erichsen JM, Woodruff JL, Grillo CA, Piroli GG, Fadel JR, Reagan LP. J Neurochem. IMPACT FACTOR: 4.2 2025 Jun;169(6):e70083. doi: 10.1111/jnc.70083. PMID: 40452372