Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums
By S. Arnold, Z. Arvanitakis, Shannon L. Macauley-Rambach, A. Koenig, Hoau Yan Wang, R. Ahima, S. Craft, S. Gandy, C. Buettner, Luke E. Stoeckel and 2 more. Nature Reviews Neurology, 2018
1,351 citations recorded by the source corpus.
Considerable overlap has been identified in the risk factors, comorbidities and putative pathophysiological mechanisms of Alzheimer disease and related dementias (ADRDs) and type 2 diabetes mellitus (T2DM), two of the most pressing epidemics of our time. Much is known about the biology of each condition, but whether T2DM and ADRDs are parallel phenomena arising from coincidental roots in ageing or synergistic diseases linked by vicious pathophysiological cycles remains unclear. Insulin resistance is a core feature of T2DM and is emerging as a potentially important feature of ADRDs. Here, we review key observations and experimental data on insulin signalling in the brain, highlighting its actions in neurons and glia. In addition, we define the concept of 'brain insulin resistance' and review the growing, although still inconsistent, literature concerning cognitive impairment and neuropathological abnormalities in T2DM, obesity and insulin resistance. Lastly, we review evidence of intrinsic brain insulin resistance in ADRDs. By expanding our understanding of the overlapping mechanisms of these conditions, we hope to accelerate the rational development of preventive, disease-modifying and symptomatic treatments for cognitive dysfunction in T2DM and ADRDs alike.
Subfields: Endocrinology, Diabetes and Metabolism, Physiology
View Paper: https://www.semanticscholar.org/paper/ed9a8eb233f013dbd4188141499fc146461fb433
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
- Sarra Setrerrahmane
- Wenwei Xie
- Ying Wang
- Hanmei Xu
- Xiaowei Chi
- Mengwei Li
Citations in the corpus
- Trends in insulin resistance: insights into mechanisms and therapeutic strategy (2022, background): “Similar to systemic IR, brain IR can be defined as failed response to insulin by brain cells,(377,378) primarily due to downregulated insulin receptors, an inability of insulin receptors to bind insulin, or dysfunction of the insulin signaling cascade.(379) Current researches have demonstrated that ”