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

ABSTRACT: 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.

SUBMITTER: Brown JM

PROVIDER: S-EPMC8368994 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

Brown Jenny M JM Bentsen Marie A MA Rausch Dylan M DM Phan Bao Anh BA Wieck Danielle D Wasanwala Huzaifa H Matsen Miles E ME Acharya Nikhil N Richardson Nicole E NE Zhao Xin X Zhai Peng P Secher Anna A Morton Gregory J GJ Pers Tune H TH Schwartz Michael W MW Scarlett Jarrad M JM

iScience 20210804 9

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 ...[more]

PMID: 34430821

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

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

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