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Glucagon‐like peptide‐1 signals to PKB and mTORC1 via the activation of the insulin‐like growth factor receptor (IGF1R) in islets of Langerhans
Author(s) -
Mostafa Norhan Mohamed El-Sayed Badr El-Din,
Moore Claire E,
Herbert Terry P
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.761.4
Subject(s) - mtorc1 , protein kinase b , microbiology and biotechnology , mapk/erk pathway , chemistry , pi3k/akt/mtor pathway , insulin like growth factor 1 receptor , transactivation , signal transduction , cancer research , receptor , growth factor , biology , biochemistry , transcription factor , gene
Objectives Glucagon‐like peptide‐1(GLP‐1) stimulates β‐cell proliferation and protects cells against cytokine induced apoptosis via activation of mTORC1 and PKB. However, it is not fully understood how GLP1 receptor activation leads to the activation of PKB/mTORC1 although it has been reported that this is mediated by EGFR transactivation. Therefore, study aims to investigate the transduction pathways by which GLP‐1 regulates PKB/mTORC1 activation. Results We showed that that AG1478 (an EGFR inhibitor), at a dose that effectively blocks EGF‐stimulated Erk phosphorylation, does not affect GLP1‐stimulated PKB or mTORC1 activation. However, diazoxide, an inhibitor of exocytosis, significantly reduced GLP1‐induced PKB and mTORC1 activation. siRNA mediated knock‐down of insulin receptor expression was unable to inhibit GLP1‐stimulated PKB or mTORC1 activation. In contrast, siRNA mediated knockdown of the IGF1 receptor effectively blocked GLP1‐stimulated PKB and mTORC1 activation. Conclusions Acute activation of PKB and mTORC1 by GLP1 is mediated via the activation of the IGF1 receptor, presumably through the autocrine effect of IGF.