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This observation led them to speculate that GLP-1 analogs might possess distinct neurotrophic properties and exert protective effects specifically on the nerve.71,395,401,402,403 Astrocytes, the most abundant cell type in adult brain nerve tissue, have recently been recognized for their pivotal role in regulating glucose and energy homeostasis.404,405,406 These cells not only respond to signals from leptin and insulin but also adapt to alterations in brain metabolism to accommodate behavioral changes by controlling glucose transport.406,407 Furthermore, astrocytes express GLP-1R, which has been found to be crucial for their proper functioning.408 Studies have shown that the loss of GLP-1R in astrocytes can impair mitochondrial integrity, leading to the dysfunction and inhibition of glucose uptake and -oxidation.407 GLP-1 inhibits glucose uptake in astrocytes and promotes beta-oxidation, which is essential for regulating energy balance in the brain and maintaining mitochondrial integrity.406 When GLP-1R is knocked out in astrocytes, it activates an integrated stress response, which affects the overall metabolic state by increasing the production of FGF21.405 This suggests that signaling through GLP-1R in astrocytes is crucial for maintaining the metabolic stability and functionality of the cells.406 FGF21 is recognized as a stress response factor that addresses mitochondrial dysfunction in cells

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Front Pharmacol 12:117 Latief U, Umar MF, Ahmad R (2019) Nrf2 protein as a therapeutic target during diethylnitrosamine-induced liver injury ameliorated by -carotene-reduced graphene oxide (C-rGO) nanocomposite