Impaired expression and insulin-stimulated phosphorylation of Akt-2 in muscle of obese patients with atypical diabetes

Aidar R. Gosmanov, Guillermo E. Umpierrez, Ana H. Karabell, Ruben Cuervo, Donald Thomason

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Abstract

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 Ser473 twofold, 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 Ser474 phosphorylation 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume287
Issue number1 50-1
DOIs
StatePublished - Jul 1 2004

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Phosphorylation
Medical problems
Muscle
Insulin
Muscles
Biopsy
Hyperglycemia
Protein Isoforms
Skeletal Muscle
Glucose Transporter Type 4
Insulin Receptor
Quadriceps Muscle
Threonine
Diabetes Mellitus
Pharmacology
Tissue
Plasmas
Glucose

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Impaired expression and insulin-stimulated phosphorylation of Akt-2 in muscle of obese patients with atypical diabetes. / Gosmanov, Aidar R.; Umpierrez, Guillermo E.; Karabell, Ana H.; Cuervo, Ruben; Thomason, Donald.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 287, No. 1 50-1, 01.07.2004.

Research output: Contribution to journalArticle

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