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Angiotensin IV Induces Phosphorylation Of Extracellular Signal‐Regulated Kinase 1/2 Via The AT 4 Receptor In 3T3‐L1 Adipocytes
Author(s) -
Jungwirth Julie Ann,
Phillips Erin E.,
Daley Brian J.,
Enderson Blaine L.,
Karlstad Michael D.
Publication year - 2010
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.24.1_supplement.lb625
Subject(s) - mapk/erk pathway , phosphorylation , insulin receptor , medicine , endocrinology , chemistry , angiotensin ii , kinase , insulin receptor substrate , receptor , signal transduction , insulin , 3t3 l1 , adipocyte , microbiology and biotechnology , biology , adipose tissue , insulin resistance , biochemistry
Angiotensin II acting via the AT 1 receptor has an inhibitory effect on the insulin‐signaling pathway in adipocytes by activation of extracellular signal‐regulated kinase (ERK 1/2) and subsequent serine phosphorylation of IRS‐1. The objective of this study was to determine if Ang IV is involved in downstream insulin‐signaling pathways by phosphorylation of ERK 1/2 via the AT 4 receptor in 3T3‐L1 adipocytes. We initially confirmed the expression of AT 4 receptors by RT‐PCR in 3T3‐L1 adipocytes. Adipocytes were incubated with various combinations of Ang IV (10 −10 M) for 10 min, AT 4 receptor inhibitor, Norleual (10 −10 M) for 1 hr, and insulin (10 −7 M) for 5 min. Cell lysates were resolved by SDS‐PAGE electrophoresis and immunoblotted with anti‐phospho‐ERK 1/2. Ang IV and insulin alone or in combination increased the phosphorylation of ERK 1/2 as compared with controls. AT 4 induced phosphorylation of ERK 1/2 was reversed by pretreatment with the novel AT 4 receptor antagonist, Norleual. Norleual attenuated Ang IV phosphorylation of ERK1/2, whereas it did not affect ERK 1/2 phosphorylation with insulin or the combination of insulin and Ang IV. This study shows that Ang IV is involved in the insulin‐signaling cascade by increasing phosphorylation of ERK 1/2, which is inhibited by AT 4 receptor blockade and is independent of the insulin receptor in adipocytes.