The Molecular Mechanism of Insulin Resistant and Glycogen Synthase Kinase 3β In the Progression of Alzheimer's disease In Type 2 Diabetes Mellitus Patients

  • Balaji Vijayam Department of Diabetology, Dr. V Balaji Dr. V Seshiah Diabetes Care and Research Institute, Aminjikarai, Chennai, Tamil Nadu, India
  • Taarika Balaji Department of Medicine, Saveetha Institute of Technical and Medical Sciences, Chennai, Tamil Nadu, India
  • Madhuri S Balaji Department of Diabetology, Dr. V Balaji Dr. V Seshiah Diabetes Care and Research Institute, Aminjikarai, Chennai, Tamil Nadu, India
  • Seshiah Veerasamy Department of Diabetology, Dr. V Balaji Dr. V Seshiah Diabetes Care and Research Institute, Aminjikarai, Chennai, Tamil Nadu, India
  • Vinothkumar Ganesan Department of Medical Research, Dr. V Balaji Dr. V Seshiah Diabetes Care and Research Institute, Aminjikarai, Chennai, Tamil Nadu, India
Keywords: Diabetes mellitus; Alzheimer's disease; Insulin resistance; GSK-3β; β amyloid; Tau protein.

Abstract

Type 2 Diabetes mellitus (T2DM) is characterized by high blood sugar caused by a lack of insulin, insulin resistance, or both. It's linked to the onset of secondary problems, which can lead to a variety of co-morbidities. Recent research has found that diabetics are more likely to acquire cognitive impairment or dementia. Diabetes is linked to a number of neurological illnesses, including Alzheimer's disease (AD). Evidence of a relationship between diabetes and AD is growing. Insulin signalling disruption in the brain has been discovered, resulting in increased tau protein phosphorylation (hyperphosphorylation), a hallmark and diagnostic of AD pathology, and the buildup of neurofibrillary tangles (NFT). Insulin malfunction in the brain has been shown to modify glycogen synthase kinase-3β (GSK-3β) activity, resulting in increased β amyloid and tau phosphorylation in diabetics. GSK-3β signalling has been implicated in the physiological and pathological processes of diabetes and AD, respectively. This could explain why diabetic individuals have a higher chance of developing AD as their diabetes progresses and they get older. Interestingly, several in vivo investigations with oral antidiabetic medications and insulin treatment in diabetic patients showed improved cognitive function and lower tau hyperphosphorylation. The relationship between T2DM and AD as it relates to amyloid and tau pathology will be discussed in this article. A better knowledge of the relationship between T2DM and AD could transform how researchers and doctors handle both diseases in the future, potentially leading to new therapies and prevention techniques.
Published
2022-01-31