Dose-Dependent Vasodilating Effects of Insulin on Adenosine-Stimulated Myocardial Blood Flow

  1. Jan Sundell12,
  2. Pirjo Nuutila12,
  3. Hanna Laine12,
  4. Matti Luotolahti3,
  5. Kari Kalliokoski1,
  6. Olli Raitakari13 and
  7. Juhani Knuuti1
  1. 1Turku PET Centre, Turku University, Turku, Finland
  2. 2Department of Medicine, Turku University, Turku, Finland
  3. 3Department of Clinical Physiology, Turku University, Turku, Finland

    Abstract

    In the peripheral vasculature, insulin induces time- and dose-dependent vasodilation. We have recently demonstrated that insulin potentiates adenosine-stimulated myocardial blood flow. However, it is unknown whether insulin’s effects on the coronary vasculature are dose dependent. In this study, we quantitated myocardial blood flow and adenosine-stimulated coronary flow (140 μg · kg−1 · min−1 for 5 min) in 10 healthy men (age, 32 ± 6 years; BMI, 24.1 ± 1.8 kg/m2) using positron emission tomography and 15O-labeled water. Hyperemic myocardial blood flow was measured in the basal state, during euglycemic physiological hyperinsulinemia (serum insulin ∼65 mU/l) and during supraphysiological hyperinsulinemia (serum insulin ∼460 mU/l). Basal myocardial blood flow was 0.84 ± 0.17 ml · g−1 · min−1. Physiological hyperinsulinemia increased the adenosine-stimulated flow by 20% (from 3.92 ± 1.17 to 4.72 ± 0.96 ml · g− 1 · min−1; P < 0.05). Supraphysiological hyperinsulinemia further enhanced the adenosine-stimulated flow by 19% (to 5.61 ± 1.03 ml · g−1 · min−1; P < 0.05). These effects were not explained by changes in systemic hemodynamics, since coronary resistance decreased during each insulin infusion (P < 0.05). In addition, hyperemic myocardial blood flow responses during insulin stimulation were positively correlated with whole-body glucose uptake. The results demonstrate that insulin is able to enhance hyperemic myocardial blood flow in a dose-dependent manner in healthy subjects. These effects might contribute to the known beneficial dose-dependent effects of insulin on myocardial ischemia.

    Footnotes

    • Address correspondence and reprint requests to Dr. Pirjo Nuutila, Turku PET Centre, Turku University Central Hospital, P.O. Box 52, FIN-20521 Turku, Finland. E-mail: pirnuu{at}utu.fi.

      Received for publication 27 June 2001 and accepted in revised form 12 December 2001.

      GIK, glucose-potassium-insulin; PET, positron emission tomography; ROI, region of interest.

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