title: Dose-dependent vasodilating effects of insulin on adenosine-stimulated myocardial blood flow.
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 microg.kg(-1).min(-1) for 5 min) in 10 healthy men (age, 32 +/- 6 years; BMI, 24.1 +/- 1.8 kg/m(2)) using positron emission tomography and (15)O-labeled water. Hyperemic myocardial blood flow was measured in the basal state, during euglycemic physiological hyperinsulinemia (serum insulin approximately 65 mU/l) and during supraphysiological hyperinsulinemia (serum insulin approximately 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.
authors.affiliation: Turku PET Centre, Turku University, Turku, Finland. Department of Medicine, Turku University, Turku, Finland.
authors.forename: Jan
authors.initials: J
authors.lastname: Sundell
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.forename: Hanna
authors.initials: H
authors.lastname: Laine
authors.forename: Matti
authors.initials: M
authors.lastname: Luotolahti
authors.forename: Kari
authors.initials: K
authors.lastname: Kalliokoski
authors.forename: Olli
authors.initials: O
authors.lastname: Raitakari
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010104:Oxygen Radioisotopes; D012016:Reference Values; D014055:Tomography, Emission-Computed; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010104:Oxygen Radioisotopes; D002784:Cholesterol; D005947:Glucose; D000241:Adenosine; D009638:Norepinephrine; D004837:Epinephrine