Premium
Glucose‐dependent insulinotropic peptide impairs insulin signaling via inducing adipocyte inflammation in glucose‐dependent insulinotropic peptide receptor‐overexpressing adipocytes
Author(s) -
Nie Yaohui,
Ma Ronald C.,
Chan Juliana C. N.,
Xu Haiyan,
Xu Gang
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/fj.11-196782
Subject(s) - medicine , endocrinology , adipocyte , gastric inhibitory polypeptide , inflammation , insulin resistance , glucose uptake , insulin , phosphorylation , insulin receptor , biology , protein kinase b , carbohydrate metabolism , chemistry , adipose tissue , microbiology and biotechnology , glucagon
Glucose‐dependent insulinotropic peptide (GIP) exerts multiple biological effects via the G‐protein‐coupled receptor GIPR, including glucose‐stimulated insulin production and secretion, cell proliferation, and antiapoptosis in pancreatic β‐cells. In an obese state, the circulating level of GIP is elevated. GIPR‐knockout mice are resistant to high‐fat‐diet‐induced obesity. The rising evidence suggests a potential role of GIP in adipocyte biology and lipid metabolism. In our study, we overexpressed GIPR in 3T3‐L1 CAR adipocytes and demonstrated that GIP impaired the physiological functions of adipocytes as a consequence of increased production of inflammatory cytokines and chemokines and phosphorylation of IkB kinase (IKK)‐β through activation of the cAMP‐PKA pathway. Activation of Jun N‐terminal kinase (JNK) pathway was also observed during GIP‐induced inflammatory responses in adipocytes. The inhibition of JNK blocked GIP‐stimulated secretion of inflammatory cytokines and chemokines, as well as phosphorylation of IKKβ. In addition, GIP‐induced inflammatory response increased basal glucose uptake but inhibited insulin‐stimulated glucose uptake. Moreover, GIP‐induced adipocyte inflammation impaired insulin signaling in adipocytes as demonstrated by a reduction of AKT phosphorylation. Our results suggest that GIP might be one of the stimuli attributable to obesity‐induced insulin resistance via the induction of adipocyte inflammation.—Nie, Y., Ma, R. C., Chan, J. C., Xu, H., Xu, G. Glucose‐dependent insulinotropic peptide impairs insulin signaling via inducing adipocyte inflammation in glucose‐dependent insulinotropic peptide receptor‐overexpressing adipocytes. FASEB J. 26, 2383‐2393 (2012). www.fasebj.org