p53 mediates impaired insulin signaling in 3T3-L1 adipocytes during hyperinsulinemia. 2014

Jyothi Kumari Posa, and Sudhagar Selvaraj, and K N Sangeetha, and Sarath Kumar Baskaran, and B S Lakshmi
Tissue culture and Drug discovery Laboratory, Centre for Biotechnology, Anna University, Chennai, 25, India.

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.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007333 Insulin Resistance Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. Insulin Sensitivity,Resistance, Insulin,Sensitivity, Insulin
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006946 Hyperinsulinism A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS. Compensatory Hyperinsulinemia,Endogenous Hyperinsulinism,Exogenous Hyperinsulinism,Hyperinsulinemia,Hyperinsulinemia, Compensatory,Hyperinsulinism, Endogenous,Hyperinsulinism, Exogenous
D000111 Acetylcysteine The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. Mercapturic Acid,Acemuc,Acetabs,Acetylcystein AL,Acetylcystein Atid,Acetylcystein Heumann,Acetylcystein Trom,Acetylcysteine Hydrochloride,Acetylcysteine Sodium,Acetylcysteine Zinc,Acetylcysteine, (D)-Isomer,Acetylcysteine, (DL)-Isomer,Acetylcysteine, Monoammonium Salt,Acetylcysteine, Monosodium Salt,Acetylin,Acetyst,Acétylcystéine GNR,Airbron,Alveolex,Azubronchin,Bisolvon NAC,Bromuc,Broncho-Fips,Broncholysin,Broncoclar,Codotussyl,Cystamucil,Dampo Mucopect,Eurespiran,Exomuc,Fabrol,Fluimucil,Fluprowit,Frekatuss,Genac,Hoestil,Ilube,Jenacystein,Jenapharm,Lantamed,Larylin NAC,Lindocetyl,M-Pectil,Muciteran,Muco Sanigen,Mucomyst,Mucosil,Mucosol,Mucosolvin,N-Acetyl-L-cysteine,N-Acetylcysteine,NAC AL,NAC Zambon,Optipect Hustengetränk,Siccoral,Siran,Solmucol,acebraus,durabronchal,mentopin Acetylcystein,Acetylcystein, mentopin,Acid, Mercapturic,Broncho Fips,BronchoFips,Hustengetränk, Optipect,Hydrochloride, Acetylcysteine,M Pectil,MPectil,Monoammonium Salt Acetylcysteine,Monosodium Salt Acetylcysteine,Mucopect, Dampo,N Acetyl L cysteine,N Acetylcysteine,NAC, Bisolvon,Sanigen, Muco,Sodium, Acetylcysteine,Zambon, NAC,Zinc, Acetylcysteine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016159 Tumor Suppressor Protein p53 Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER. p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53
D016166 Free Radical Scavengers Substances that eliminate free radicals. Among other effects, they protect PANCREATIC ISLETS against damage by CYTOKINES and prevent myocardial and pulmonary REPERFUSION INJURY. Free Radical Scavenger,Radical Scavenger, Free,Scavenger, Free Radical,Scavengers, Free Radical

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