Troglitazone enhances glucose uptake induced by α-adrenoceptor stimulation via phosphatidylinositol 3-kinase in rat heart

Jun Yoshioka, Hideo Kusuoka, Kenichi Imahashi, Katsuji Hashimoto, Masatsugu Hori, Taichiro Terakawa, Tsunehiko Nishimura

Research output: Contribution to journalArticle

Abstract

1. Thiazolidinedione-derived agents have been reported to act as insulin sensitizers by augmenting insulin-dependent stimulation of phosphatidylinositol 3-kinase (PI3K) activity in a specific manner. It has been suggested that α-adrenoceptor stimulation mediates glucose uptake through PI3K in the heart. 2. To elucidate whether the thiazolidinedione-derived agent troglitazone (TRO) affects glucose uptake induced by α-adrenoceptor stimulation through PI3K, the rate of glucose uptake was quantified from the rate of accumulation of sugar phosphate (d[SP]/dt) using [31P] nuclear magnetic resonance spectroscopy after substitution of glucose with 2-deoxyglucose in rat perfused heart. Hearts were stimulated with 100 μmol/L phenylephrine plus 10 μmol/L propranolol (α-adrenoceptor stimulation), or 1 μmol/L isoproterenol plus 10 μmol/L phentolamine (β-adrenoceptor stimulation). 3. The d[SP]/dt in the α- and β-adrenoceptor-stimulated groups (0.45 ± 0.06 and 0.42 ± 0.04 μmol/min per g, respectively) was higher than that of the control group (0.27 ± 0.02 μmol/min per g; P < 0.01). The addition of 2 μg/mL troglitazone to α-adrenoceptor stimulation augmented d[SP]/dt (0.72 ± 0.08 μmol/min per g; P < 0.05 vs the α-adrenoceptor-stimulated group), which was effectively blocked by 3 μmol/L wortmannin (0.35 ± 0.06 μmol/min per g; P < 0.01 vs troglitazone + α-adrenoceptor stimulation group). However, addition of troglitazone to β-adrenoceptor stimulation did not alter d[SP]/dt (0.33 ± 0.02 μmol/min per g; P = NS vs the β-adrenoceptor-stimulated group). 4. These results indicate that troglitazone acutely enhances α-adrenoceptor stimulation on glucose uptake through a PI3K-dependent pathway, thus possibly improving glucose utilization in a catecholamine-released state.

Original languageEnglish (US)
Pages (from-to)752-757
Number of pages6
JournalClinical and Experimental Pharmacology and Physiology
Volume28
Issue number9
DOIs
StatePublished - Dec 1 2001

Keywords

  • Catecholamine
  • Glucose uptake
  • Phosphoinositide 3-kinase
  • Rat isolated heart
  • Troglitazone

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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