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Tumminia, A., Vinciguerra, F., Parisi, M., & Frittitta, L. (2018). Type 2 Diabetes Mellitus and Alzheimer’s Disease: Role of Insulin Signalling and Therapeutic Implications. International journal of molecular sciences, 19(11), 3306. https://doi.org/10.3390/ijms19113306
Insulin, a key hormone produced in the pancreas that regulates glucose within the bloodstream, has long been attributed to neuronal survival, or the ability of neurons to function, as well as basic brain activity. As a result of the functions mentioned in the previous sentence, failures for insulin to perform specific chemical reactions have been correlated to the prognosis of diseases such as Type 2 Diabetes Mellitus (T2DM), or high levels of blood sugar, and Alzheimer’s Disease, a neurodegenerative disorder that impacts memory. This article is a literature review that goes over the main connection between both Alzheimer’s and T2DM as well as the potential for current antidiabetic drugs to be used to ease symptoms of Alzheimer’s.
When insulin binds to specific receptors called insulin receptors (IR) present in the central nervous system (including the brain and spinal cord), it exerts properties that can positively influence human emotion and cognitive functions such as memory and attention. When insulin adds phosphate groups to insulin receptor substrates, it can prevent the accumulation of specific proteins that have been linked with the onset of Alzheimer’s Disease.
Recent research has shown that dysfunction in insulin binding prevents tau proteins, which help stabilise nerve cells within the brain, from being activated. Defects in the way insulin breaks down can also lead to the buildup of amyloid-β peptides, proteins that have antimicrobial activity and protect against the production of reactive oxygen species (ROS), reactive molecules that are produced in response to environmental changes. Although its effects are positive, when there is an excessive amount of amyloid-β, the effects become negative as the glymphatic system that is responsible for cleaning out proteins in the brain is not able to get rid of the large quantities of amyloid-β. This aggregation will eventually lead to amyloid-β-induced neuron degeneration. An increase in both amyloid-β plaques and the inactivated tau proteins can cause the development of Alzheimer’s Disease, which demonstrates the importance of maintaining stable insulin regulatory control within the human body.
There have been a variety of antidiabetic drugs that have been hypothesised to mitigate the dangerous symptoms attributed to Alzheimer’s Disease. Metformin, for example, has demonstrated its ability to be administered across several regions of the brain and restore mitochondrial function. This is important as mitochondria are responsible for creating the body’s source of energy, or ATP, and has also been shown to decrease ROS. Since an increase in ROS can lead to the body not responding to and becoming resistant to insulin, a cause of T2DM, the decrease in ROS will allow for insulin to continue processing at its normal rate. However, scientists have shown that metformin can lead to mild cognitive impairment, so more research is necessary to truly understand metformin’s ability to treat Alzheimer’s. Another drug is insulin, which can benefit memory and learning skills, preserving the neurons’ ability to alter themselves to adapt to specific situations. Despite this, it has been linked to hypoglycemia (low blood sugar levels).
Thiazolidinediones, a class of receptor drugs that can improve insulin sensitivity throughout the human body, may play a crucial role in protecting memory and restoring cognitive function. In fact, pioglitazone is a drug that is commercially available for use to reduce symptoms of Alzheimer’s. Another class of drugs is sulfonylureas, which can stimulate insulin release in the brain. It has been demonstrated that sulfonylureas can protect neurons from degeneration caused by amyloid-β, but some other sources demonstrated that sulfonylureas has no effect on dementia over long periods of time. An additional class would be glucagon-like peptide-1 receptor agonists, which are abbreviated to GLP-1 agonists. This peptide class can enhance the secretion of insulin while diminishing the secretion of glucagon, leading to a decrease in blood sugar levels. This increase in insulin helps prevent damage to the brain caused by amyloid-β, but is also a disadvantage as the lower blood sugar levels can lead to its own symptoms such as blurred vision and a lack of immunity to infection.
Summarised by Brenton Lee
Works Cited:
The Amyloid Beta Peptide: A Chemist’s Perspective. Role in Alzheimer’s … https://centaur.reading.ac.uk/30230/2/AbetaRevisednew%2520-IWH%2520%25281%2529.pdf.
“Hyperglycaemia (High Blood Sugar).” NHS Inform, https://www.nhsinform.scot/illnesses-and-conditions/blood-and-lymph/hyperglycaemia-high-blood-sugar.
“An Overview of Insulin.” Medical News Today, MediLexicon International, https://www.medicalnewstoday.com/articles/323760.
“Type 2 Diabetes Mellitus.” Harvard Health, 23 Feb. 2022, https://www.health.harvard.edu/a_to_z/type-2-diabetes-mellitus-a-to-z.
“Type 2 Diabetes: Too Much Glucagon?” ScienceDaily, ScienceDaily, 20 Apr. 2020, https://www.sciencedaily.com/releases/2020/04/200420110018.htm#
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