title: p53 mediates impaired insulin signaling in 3T3-L1 adipocytes during hyperinsulinemia.
abstract: Hyperinsulinemia is being implicated in the development of insulin resistance but remains poorly understood. The present study focuses on p53-mediated impaired insulin signaling by hyperinsulinemia in 3T3-L1 adipocytes. Hyperinsulinemia impairs insulin-stimulated glucose uptake and its cellular signaling in a dose- and time-dependent manner. An increased level of reactive oxygen species (ROS) and stress response signals were observed, and quenching of the ROS by an antioxidant N-acetylcysteine (NAC) did not revert impaired insulin sensitivity. The tumor suppressor p53 has emerged as a crucial factor in the metabolic adaptation of cancer cells under nutritional starvation and is being studied in the development of insulin resistance in adipocytes at physiological level. Interestingly, we observed hyperinsulinemia-enhanced p53 level in a time-dependent manner without exhibiting cytotoxicity. Transient knockdown of p53 partially improved insulin sensitivity revealing a novel link between p53 and insulin signaling in adipocytes. The findings suggest that hyperinsulinemia-induced p53 impairs insulin sensitivity in 3T3-L1 adipocytes.
authors.affiliation: Tissue culture and Drug discovery Laboratory, Centre for Biotechnology, Anna University, Chennai, 25, India.
authors.forename: Jyothi Kumari
authors.initials: JK
authors.lastname: Posa
authors.forename: Sudhagar
authors.initials: S
authors.lastname: Selvaraj
authors.forename: K N
authors.initials: KN
authors.lastname: Sangeetha
authors.forename: Sarath Kumar
authors.initials: SK
authors.lastname: Baskaran
authors.forename: B S
authors.initials: BS
authors.lastname: Lakshmi
mesh_terms: D041721:3T3-L1 Cells; D000111:Acetylcysteine / Q000494:pharmacology; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D007328:Insulin; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D005947:Glucose; D000111:Acetylcysteine
keywords: NAC; ROS; hyperinsulinemia; insulin resistance; insulin signaling; p53