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. / Brown, Jenny M.; Bentsen, Marie A.; Rausch, Dylan M.; Phan, Bao Anh; Wieck, Danielle; Wasanwala, Huzaifa; Matsen, Miles E.; Acharya, Nikhil; Richardson, Nicole E.; Zhao, Xin; Zhai, Peng; Secher, Anna; Morton, Gregory J.; Pers, Tune H.; Schwartz, Michael W.; Scarlett, Jarrad M.
In: iScience, Vol. 24, No. 9, 102944, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Role of hypothalamic MAPK/ERK signaling and central action of FGF1 in diabetes remission
AU - Brown, Jenny M.
AU - Bentsen, Marie A.
AU - Rausch, Dylan M.
AU - Phan, Bao Anh
AU - Wieck, Danielle
AU - Wasanwala, Huzaifa
AU - Matsen, Miles E.
AU - Acharya, Nikhil
AU - Richardson, Nicole E.
AU - Zhao, Xin
AU - Zhai, Peng
AU - Secher, Anna
AU - Morton, Gregory J.
AU - Pers, Tune H.
AU - Schwartz, Michael W.
AU - Scarlett, Jarrad M.
N1 - Publisher Copyright: © 2021 The Authors
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Diabetology
KW - Molecular biology
KW - Molecular neuroscience
U2 - 10.1016/j.isci.2021.102944
DO - 10.1016/j.isci.2021.102944
M3 - Journal article
C2 - 34430821
AN - SCOPUS:85112585566
VL - 24
JO - iScience
JF - iScience
SN - 2589-0042
IS - 9
M1 - 102944
ER -
ID: 280176642