Effects of chronic Akt activation on glucose uptake in the heart

Takashi Matsui, Tomohisa Nagoshi, Eun Gyoung Hong, Ivan Luptak, Kirsten Hartil, Ling Li, Naira Gorovits, Maureen J. Charron, Jason K. Kim, Rong Tian, Anthony Rosenzweig

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43 Scopus citations

Abstract

Acute activation of the serine-threonine kinase Akt is cardioprotective and increases glucose uptake, at least in part, through enhanced expression of GLUT4 on the sarcolemma. The effects of chronic Akt activation on glucose uptake in the heart remain unclear. To address this issue, we examined the effects of chronic Akt activation on glucose uptake, glycogen storage, and relevant glucose transporters in the hearts of transgenic mice. We found that chronic cardiac activation of Akt led to a substantial increase in the rate of basal glucose uptake (P < 0.05) but blunted the response to insulin (1.9 vs. 18.1-fold increase compared with baseline) using NMR in ex vivo perfused heart. Basal glucose uptake was also increased in Akt transgenic mice in vivo (P < 0.005). These changes were associated with an increase on glycogen deposition, examined with histochemical staining, biochemical (>6-fold, P < 0.001) and in vivo radioactive (5-fold, P < 0.01) assays. Studies in chimeric hearts of female X-linked transgenic Akt mice suggested that increased glycogen deposition occurred as a cell autonomous effect of transgene expression. Interestingly, although sarcolemmal GLUT1 was not significantly altered, chronic Akt activation actually decreased plasma membrane GLUT4. Moreover, intracellular pools of GLUT1 were modestly reduced, whereas intracellular GLUT4 was substantially reduced. It seems likely that neither GLUT1 nor GLUT4 explains the increase in basal glucose uptake but that these reductions contribute to the loss of insulin responsiveness that we observed. These data demonstrate that chronic Akt activation increases basal glucose uptake and glycogen deposition while inhibiting the response to insulin.

Original languageEnglish (US)
Pages (from-to)E789-E797
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume290
Issue number5
DOIs
StatePublished - May 1 2006

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Keywords

  • Glucose transporters
  • Heart
  • Transgenic mice

ASJC Scopus subject areas

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

Cite this

Matsui, T., Nagoshi, T., Hong, E. G., Luptak, I., Hartil, K., Li, L., Gorovits, N., Charron, M. J., Kim, J. K., Tian, R., & Rosenzweig, A. (2006). Effects of chronic Akt activation on glucose uptake in the heart. American Journal of Physiology - Endocrinology and Metabolism, 290(5), E789-E797. https://doi.org/10.1152/ajpendo.00564.2004