Inside the diabetic brain: Insulin resistance and molecular mechanism associated with cognitive impairment and its possible therapeutic strategies

Type 2 diabetes mellitus (T2DM) the most prevalent metabolic disease that has evolved into a major public health issue. Concerning about its secondary complications, a growing body of evidence links T2DM to cognitive impairment and neurodegenerative disorders. The underlying pathology behind this secondary complication disease is yet to be fully known. Nonetheless, they are likely to be associated with poor insulin signaling as a result of insulin resistance. We have combed through a rising body of literature on insulin signaling in the normal and diabetic brains along with various factors like insulin resistance, hyperglycemia, obesity, oxidative stress, neuroinflammation and A beta plaques which can act independently or synergistically to link T2DM with cognitive impairments. Finally, we explored several pharmacological and non-pharmacological methods in the hopes of accelerating the rational development of medications for cognitive impairment in T2DM by better understanding these shared pathways.

Automated summary

Type 2 diabetes mellitus (T2DM) is a common metabolic disease and a major public health issue. There is increasing evidence linking T2DM to cognitive impairment and neurodegenerative disorders. The underlying pathology of this secondary complication is likely to be associated with poor insulin signaling due to insulin resistance. This article reviews the literature on insulin signaling in normal and diabetic brains, as well as various factors such as insulin resistance, hyperglycemia, obesity, oxidative stress, neuroinflammation, and A beta plaques, which can independently or synergistically connect T2DM with cognitive impairments. The article also explores pharmacological and non-pharmacological methods to accelerate the development of medications for cognitive impairment in T2DM by better understanding these shared pathways.