p53 Mediates impaired insulin signaling in 3T3-L1 adipocytes during hyperinsulinemia

• Published in: Cell biology international Vol. 38; no. 7; pp. 818 - 824
• Main Authors: Posa, Jyothi Kumari, Selvaraj, Sudhagar, Sangeetha, K. N., Baskaran, Sarath Kumar, Lakshmi, B.S.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.07.2014; Wiley Subscription Services, Inc
• Subjects: 3T3-L1 Cells; Acetylcysteine - pharmacology; Adipocytes; Adipocytes - cytology; Adipocytes - metabolism; Animals; Cell Differentiation - drug effects; Free Radical Scavengers - pharmacology; Glucose - metabolism; Hyperglycemia; hyperinsulinemia; Hyperinsulinism - metabolism; Hyperinsulinism - pathology; Insulin; Insulin - metabolism; Insulin Resistance; insulin signaling; Mice; NAC; p53; Reactive Oxygen Species - metabolism; RNA Interference; RNA, Small Interfering - metabolism; ROS; Signal Transduction - drug effects; Tumor Suppressor Protein p53 - antagonists & inhibitors; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; NAC; insulin signaling; hyperinsulinemia; insulin resistance; ROS; p53
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1002/cbin.10275

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.