Role of hypothalamic MAPK/ERK signaling and central action of FGF1 in diabetes remission
| Autor: | Nikhil K. Acharya, Jenny M. Brown, Bao Anh Phan, Danielle Wieck, Miles E. Matsen, Dylan M. Rausch, Marie A. Bentsen, Huzaifa Wasanwala, Anna Secher, Peng Zhai, Tune H. Pers, Jarrad M. Scarlett, Nicole E. Richardson, Xin Zhao, Michael W. Schwartz, Gregory J. Morton |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | iScience Brown, J M, Bentsen, M A, Rausch, D M, Phan, B A, Wieck, D, Wasanwala, H, Matsen, M E, Acharya, N, Richardson, N E, Zhao, X, Zhai, P, Secher, A, Morton, G J, Pers, T H, Schwartz, M W & Scarlett, J M 2021, ' Role of hypothalamic MAPK/ERK signaling and central action of FGF1 in diabetes remission ', iScience, vol. 24, no. 9, 102944 . https://doi.org/10.1016/j.isci.2021.102944 iScience, Vol 24, Iss 9, Pp 102944-(2021) |
| ISSN: | 2589-0042 |
| Popis: | Summary The capacity of the brain to elicit sustained remission of hyperglycemia in rodent models of type 2 diabetes following intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) is well established. Here, we show that following icv FGF1 injection, hypothalamic signaling by extracellular signal-regulated kinases 1 and 2 (ERK1/2), members of the mitogen-activated protein kinase (MAPK) family, is induced for at least 24 h. Further, we show that this prolonged response is required for the sustained antidiabetic action of FGF1 since it is abolished by sustained (but not acute) pharmacologic blockade of hypothalamic MAPK/ERK signaling. We also demonstrate that FGF1 R50E, a FGF1 mutant that activates FGF receptors but induces only transient hypothalamic MAPK/ERK signaling, fails to mimic the sustained glucose lowering induced by FGF1. These data identify sustained activation of hypothalamic MAPK/ERK signaling as playing an essential role in the mechanism underlying diabetes remission induced by icv FGF1 administration. Graphical abstract Highlights • FGF1 action in the brain induces remission of diabetic hyperglycemia • FGF1 induces sustained activation of hypothalamic MAPK/ERK signaling • Blockade of hypothalamic MAPK/ERK signaling abolishes the antidiabetic action of FGF1 • FGF1 increases hypothalamic astrocyte-neuron interaction by transcriptomic analysis Molecular biology; Molecular neuroscience; Diabetology |
| Databáze: | OpenAIRE |
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