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Chronic hyperinsulinemia sensitizes myocytes to hyperglycemia‐induced cell death
Author(s) -
Harmancey Romain,
Lubrano Genna,
Lam Truong N.,
Taegtmeyer Heinrich
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.869.24
Subject(s) - glut4 , hyperinsulinemia , medicine , glut1 , glucose transporter , insulin , myocyte , endocrinology , glucose uptake , carbohydrate metabolism , stimulation , insulin resistance
Recent clinical trials have reported that intensive glucose lowering therapy in type 2 diabetic patients increases death from cardiovascular causes. We therefore investigated whether aggressive insulin therapy sensitizes myocytes to glucose toxicity. Rat L6 myocytes, cultured in low (5.5 mM) glucose conditions, were treated every 24 hours with insulin. After 5 days of treatment, the rates of glucose uptake were measured, and the expression of the glucose transporters GLUT1 and GLUT4 quantified by real‐time PCR and western blotting. Another set of cells was incubated in hyperglycemic (30 mM) conditions, and the activity of the proapoptotic caspase‐3 was measured by spectrophotometry. Chronic insulin treatment increased the rates of glucose uptake compared to non‐treated cells. This increase, which was associated to higher expression levels of both GLUT1 and GLUT4, could not be further potentiated by acute insulin stimulation. In addition, the cells chronically treated with insulin also exhibited an increase in caspase‐3 activity when incubated with high glucose concentrations. In conclusion, simulated chronic hyperinsulinemia upregulates glucose transporters in myocytes, and the ensuing increase in glucose uptake is associated with a sensitization of the cells to hyperglycemia‐induced cell death. This work provides direct evidence for toxic effects of increased glucose metabolism in muscle cells.