title: cAMP antagonizes ERK-dependent antiapoptotic action of insulin.
abstract: Insulin has antiapoptotic activity in various cell types. However, the signaling pathways underlying the antiapoptotic activity of insulin is not yet known. This study was conducted to determine if cAMP affects the antiapoptotic activity of insulin and the activity of PI3K and ERK in CHO cells expressing human insulin receptors (CHO-IR). Insulin-stimulated ERK activity was completely suppressed by cAMP-elevating agents like as pertussis toxin (Ptx) and cholera toxin (Ctx) after 4 h treatment. Insulin-stimulated PKB/Akt activity was not affected at all. Ptx treatment together with insulin increased the number of apoptotic cells and the degree of DNA fragmentation. Ctx or 8-brcAMP treatment also increased the number of apoptotic cells and stimulated the cleavage of caspase-3 and the hydrolysis of PARP. Taken together, cAMP antagonizes the antiapoptotic activity of insulin and the main target molecule of cAMP in this process is likely ERK, not PI3K-dependent PKB/Akt.
authors.affiliation: Department of Medicine, School of Medicine and Institute of Medical Science, Jeju National University, Korea.
authors.forename: Zhi Gang
authors.initials: ZG
authors.lastname: Cui
authors.forename: Na Young
authors.initials: NY
authors.lastname: Hong
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Kang
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Young Ki
authors.initials: YK
authors.lastname: Lee
authors.forename: Deok Bae
authors.initials: DB
authors.lastname: Park
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D016466:CHO Cells; D002772:Cholera Toxin / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D007328:Insulin; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; C435941:INSR protein, human; D011972:Receptor, Insulin; D048049:Extracellular Signal-Regulated MAP Kinases