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Role of hypothalamic MAPK/ERK signaling and central action of FGF1 in diabetes remission.

iScience (2021-08-26)
Jenny M Brown, Marie A Bentsen, Dylan M Rausch, Bao Anh Phan, Danielle Wieck, Huzaifa Wasanwala, Miles E Matsen, Nikhil Acharya, Nicole E Richardson, Xin Zhao, Peng Zhai, Anna Secher, Gregory J Morton, Tune H Pers, Michael W Schwartz, Jarrad M Scarlett
RÉSUMÉ

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.

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Albumine de sérum bovin, heat shock fraction, pH 7, ≥98%
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Triton X-100, BioXtra
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U0126, U0126, CAS 109511-58-2, is a potent and specific inhibitor of MEK1 (IC₅₀ = 72 nM) and MEK2 (IC₅₀ = 58 nM). The inhibition is noncompetitive with respect to both ATP and ERK.
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Anticorps monoclonal anti-protéine acide fibrillaire gliale (GFAP) antibody produced in mouse, clone G-A-5, purified from hybridoma cell culture