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Arcuate nucleus injection of anti‐insulin affibody prevents sympathetic response to circulating insulin
Author(s) -
Luckett Brittany,
Frielle Jennifer,
Wolfgang Lawrence,
Stocker Sean D.
Publication year - 2012
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.26.1_supplement.705.5
Subject(s) - insulin , medicine , endocrinology , arc (geometry) , chemistry , mathematics , geometry
Insulin contributes to cardiovascular dysfunction by central actions to increase sympathetic nerve activity (SNA). The arcuate nucleus (ARC) abundantly expresses insulin receptors, and direct ARC injection of insulin raises lumbar SNA (LSNA). Therefore, we hypothesized that peripheral insulin acts on ARC neurons to increase LSNA and tested this by using an anti‐insulin affibody to neutralize insulin. To test the efficacy of the affibody, anesthetized Sprague‐Dawley rats received bilateral ARC injection (40nL) of either an anti‐insulin (1μg) or control affibody (1μg) ~10 min before ARC injection of insulin (4μU). The anti‐insulin vs control affibody abolished the increased LSNA (120 min: 99±1% vs 128 ±8%, n=4; P<0.05). Blood pressure and heart rate were similar between groups. Second, ARC injection of anti‐insulin vs control affibody prevented the increased LSNA during a hyperinsulinemic‐euglycemic clamp (7.5mU/kg/min, IV; 114±5% vs 153±15%, n=5–6; P<0.05). Yet, ARC injection of gabazine elevated LSNA in both anti‐insulin vs control animals suggesting the affibody does not generally inhibit ARC neurons. These results indicate circulating insulin acts directly on ARC neurons to increase SNA. Grant Funding Source : HL090826 , APS UGSRF