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Cerebral insulin, insulin signaling pathway, and brain angiogenesis

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Abstract

Insulin performs unique non-metabolic functions within the brain. Broadly speaking, two major areas of these functions are those related to brain endothelial cells and the blood–brain barrier (BBB) function, and those related to behavioral effects, like cognition in disease states (Alzheimer’s disease, AD) and in health. Recent studies showed that both these functions are associated with brain angiogenesis. These findings raise interesting questions such as how they are linked to each other and whether modifying brain angiogenesis by targeting certain insulin signaling pathways could be an effective strategy to treat dementia as in AD, or even to help secure healthy longevity. The two canonical downstream pathways involved in mediating the insulin signaling pathway, the phosphoinositide-3 kinase (PI3K), and mitogen-activated protein kinase (MAPK) cascades, in the brain are supposed to be similar to those in the periphery. PI3K and MAPK pathways play important roles in angiogenesis. Both are involved in stimulating hypoxia inducible factor (HIF) in angiogenesis and could be activated by the insulin signaling pathway. This suggests that PI3K and MAPK pathways might act as cross-talk between the insulin signaling pathway and the angiogenesis pathway in brain. But the cerebral insulin, insulin signaling pathway, and the detailed mechanism in the connection of insulin signaling pathway, brain angiogenesis pathway, and healthy aging or dementias are still mostly not clear and need further studies.

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Acknowledgments

We thank Joseph C. LaManna, Kui Xu and Girriso Benderro for their expertise, and Suzanne Foss, all from Case Western Reserve University, Cleveland OH, USA for help in editing the manuscript

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Authors and Affiliations

  1. Department of Geriatrics, Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Yi Zeng

  2. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China

    Le Zhang

  3. Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Zhiping Hu

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Correspondence to Le Zhang.

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This work was supported by the National Natural Science Foundation of China (30600199 and 81200838), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry ([2013]1972) and the Foundation of Hunan Science and Technology Committee (2014FJ3138).

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Zeng, Y., Zhang, L. & Hu, Z. Cerebral insulin, insulin signaling pathway, and brain angiogenesis. Neurol Sci 37, 9–16 (2016). https://doi.org/10.1007/s10072-015-2386-8

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