Hyperglycemia-induced activation of human T-lymphocytes with de novo emergence of insulin receptors and generation of reactive oxygen species.
Upon activation by phytohemagglutine (PHA), T-lymphocytes (T-cells) express receptors for growth factors, insulin, IGF-1 and IL2 and become insulin sensitive. Diabetic ketoacidosis (DKA) is associated with in vivo emergence of these growth factor receptors without incubation with PHA. As DKA consists of multiple metabolic alterations, in addition to hyperglycemia, we investigated the in vitro effect of different concentrations of glucose (5, 15, and 30 mM) in isolated CD4 of human T-cells at various time intervals (0, 24, 48, and 72 h). Hyperglycemia, but not euglycemia, resulted in de novo emergence of growth factor receptors in a dose- and time-dependent fashion. The activation was also associated with incremental changes in GLUT 4, IRS-1, proinflammatory cytokines, and oxidative stress components. We propose that activation of T-cells with development of insulin receptors in hyperglycemic conditions may serve as a mechanism for control of glucose entry into these cells, thus, protecting them against glucose toxicity.
Stentz
Frankie B
FB
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Kitabchi
Abbas E
AE
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015227:Lipid Peroxidation; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism; D010835:Phytohemagglutinins / Q000378:metabolism; D017382:Reactive Oxygen Species; D011972:Receptor, Insulin / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors
D016207:Cytokines; D051275:Glucose Transporter Type 4; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D007376:Interleukin-2; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D010835:Phytohemagglutinins; D017382:Reactive Oxygen Species; D017978:Receptors, Growth Factor; C495692:SLC2A4 protein, human; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D005947:Glucose