Insulin-like peptides signaling in Alzheimer's disease: on the road to alternative therapeutics

Trueba-Saiz, Ángel; Torres‐Alemán, Ignacio

doi:10.1016/j.cobeha.2015.11.013

Cited by 2 publications

(1 citation statement)

References 89 publications

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“…These observations may open a new path for future therapeutic approaches for brain complications in diabetes (49) and for diabetes-like pathology in neurodegenerative diseases such as Alzheimer dementia (50).…”

Section: Discussionmentioning

confidence: 93%

Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I

et al. 2016

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Brain activity requires a flux of glucose to active regions to sustain increased metabolic demands. Insulin, the main regulator of glucose handling in the body, has been traditionally considered not to intervene in this process. However, we now report that insulin modulates brain glucose metabolism by acting on astrocytes in concert with IGF-I. The cooperation of insulin and IGF-I is needed to recover neuronal activity after hypoglycemia. Analysis of underlying mechanisms show that the combined action of IGF-I and insulin synergistically stimulates a mitogen-activated protein kinase/protein kinase D pathway resulting in translocation of GLUT1 to the cell membrane through multiple protein-protein interactions involving the scaffolding protein GAIP-interacting protein C terminus and the GTPase RAC1. Our observations identify insulin-like peptides as physiological modulators of brain glucose handling, providing further support to consider the brain as a target organ in diabetes.

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Section: Discussionmentioning

confidence: 93%