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Insulin in the arcuate nucleus increases sympathetic nerve activity via extracellular signal‐regulated kinases (686.12)
Author(s) -
Streiff Cole,
Cassaglia Priscila,
Shi Zhigang,
Li Baoxin,
Brooks Virginia
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.686.12
Subject(s) - endocrinology , medicine , insulin , mapk/erk pathway , insulin receptor , chemistry , insulin resistance , kinase , biochemistry
Intracerebroventricular (ICV) insulin infusion increases SNA, which can be prevented by prior brain inhibition of ERK activation; however, the brain site of ERK activation is unknown. To test the hypothesis that ERK is involved within the site of action of insulin, the arcuate nucleus (ArcN), we first determined if bilateral ArcN nanoinjection of the ERK inhibitor PD98059 (60 nL of 0.5 mM/L) prevents the increases in lumbar SNA (LSNA) induced by ArcN insulin (60 pU in 30 nL) in α‐chloralose‐anesthetized male rats. ArcN insulin increased LSNA from 101±3 to 130±6 % control (P<0.05; n=5). PD98059 alone had no effects (108±9 to 112±8 % control), but subsequent ArcN insulin failed to increase LSNA (105±7 to 102±2 % control; n=4). In contrast, ArcN insulin still increased LSNA (106±4 to 147±24 % control; P<0.05) following ArcN blockade of PI3K (LY294002; 60 nL of 0.5 mM/L; n=5). Next, insulin (100 µU/min; n=3) or aCSF (0.6 µL/min; n=3) was infused ICV for 35 min, followed by dual ArcN immunohistochemistry of activated ERK and the insulin receptor (InsR). While there was no difference in the number of ArcN InsR immunoreactive (‐ir) neurons between insulin‐infused (223±17) and aCSF‐infused (263±21) rats, activated ERK‐ir was found only in the ArcN of insulin infused rats (137±13 vs. 7±2 neurons; P<0.05), with 34±6% of InsR‐ir neurons also expressing activated ERK‐ir. In conclusion, ArcN insulin increases LSNA via ERK signaling, possibly within the InsR‐responding neuron. Grant Funding Source : Supported by HL088552 and AHA.