Impaired expression and insulin-stimulated phosphorylation of Akt-2 in muscle of obese patients with atypical diabetes
| Autor: | Ana H. Karabell, Ruben Cuervo, Donald B. Thomason, Guillermo E. Umpierrez, Aidar R. Gosmanov |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male medicine.medical_specialty Monosaccharide Transport Proteins Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Muscle Proteins Biology Diabetes Complications Physiology (medical) Insulin receptor substrate Internal medicine Diabetes Mellitus medicine Humans Insulin Obesity Phosphorylation Muscle Skeletal Protein kinase B Pancreatic hormone Glucose Transporter Type 4 Skeletal muscle medicine.disease Insulin receptor Endocrinology medicine.anatomical_structure Hyperglycemia biology.protein Female |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 287:E8-E15 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | Although a pharmacological dose of insulin produces a dramatic increase in phosphorylation and activity of Akt isoforms 1 and 2 in mammalian skeletal muscle, few studies have examined the effect of physiological concentrations of insulin on the phosphorylation of Akt-1 and -2 in normal and diabetic tissue. This study examined the patterns of insulin-stimulated Akt isoform phosphorylation and protein expression in muscle biopsies obtained from obese patients with atypical diabetes immediately after a hyperglycemic crisis and again after near-normoglycemic remission. In obese patients with new-onset diabetes mellitus presenting with hyperglycemic crisis (plasma glucose 30.5 ± 4.8 mM), in vitro stimulation of vastus lateralis muscle biopsies with 100 μU/ml (0.6 nM) insulin increased insulin receptor phosphorylation threefold and Akt-1 phosphorylation on Ser473twofold, whereas Akt-2 phosphorylation was not stimulated. After 10-wk intensive insulin therapy that led to near-normoglycemic remission and discontinuation of insulin therapy, both Akt-2 expression and insulin-stimulated Akt-2 Ser474phosphorylation doubled. Hyperglycemic crisis did not affect insulin-stimulated threonine phosphorylation of either Akt-1 or Akt-2. The decreased Akt-2 expression at presentation was accompanied by reduced GLUT4 protein expression and increased expression of enzymes counterregulatory to insulin action. Thus a physiological concentration of insulin stimulated Akt-1 and Akt-2 phosphorylation in human skeletal muscle in the absence of hyperglycemia, but Akt-2 expression and stimulation appeared to be impaired in muscle of obese patients with atypical diabetes presenting with severe hyperglycemia. |
| Databáze: | OpenAIRE |
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