title: Insulin-induced increment of coronary flow reserve is not abolished by dexamethasone in healthy young men.
abstract: Hyperinsulinemia is a risk factor for coronary artery disease. Previous studies have reported that hyperinsulinemia increases cardiac and skeletal muscle sympathetic nerve activity and skeletal muscle blood flow in normal subjects. However, little is known about insulin's effects on myocardial blood flow in humans. The purpose of this study was to investigate whether physiological hyperinsulinemia affects myocardial blood flow and flow reserve in healthy subjects. Additionally, the role of the sympathetic nervous system in regulating insulin's effects on coronary perfusion was tested. We used positron emission tomography and oxygen-15-labeled water to measure myocardial blood flow and coronary flow reserve in 16 healthy nonobese men (age, 34 +/- 4 yr; maximal aerobic capacity, 32 +/- 3 mL x g(-1) x min(-1); blood pressure, 118 +/- 10/65 +/- 8 mm Hg) at fasting and during euglycemic hyperinsulinemic clamp (1 mU x kg(-1) x min(-1) for 80 min). To study the role of the sympathetic nervous system, each subject was studied twice: once after administration of dexamethasone (dexa+) for 2 days (2 mg per day) and once without previous medication (dexa-). All studied subjects had normal left ventricular mass, function, and findings in stress echocardiography. Resting myocardial blood flow was 0.76 +/- 0.19 mL x g(-1) x min(-1), and a significant increase in flow was detected after adenosine infusion (140 microg/kg x min for 5 min i.v.), both in the basal fasting state (P < 0.001) and during hyperinsulinemia (P < 0.001). However, the flow response to adenosine was significantly higher during hyperinsulinemia, thus leading to a higher hyperemic flow (3.38 +/- 0.97 vs. 4.28 +/- 1.57 mL x g(-1) x min(-1), basal vs. hyperinsulinemic, P < 0.01) and higher coronary flow reserve (4.6 +/- 1.2 vs. 5.8 +/- 1.9, respectively, P < 0.05). Pretreatment with dexamethasone did not significantly change the resting blood flow [0.72 +/- 0.22 vs. 0.76 +/- 0.19 mL x g(-1) x min(-1), dexa+ vs. dexa-, not significant (NS)], the adenosine stimulated flow (3.56 +/- 1.49 vs. 3.38 +/- 0.97 mL x g(-1) x min(-1), respectively, NS), or the hyperinsulinemic adenosine-stimulated blood flow (4.68 +/- 1.74 vs. 4.28 +/- 1.57 mL x g(-1) x min(-1), respectively, NS). Coronary flow reserves in the basal state (5.3 +/- 2.7 vs. 4.6 +/- 1.2 mL x g(-1) x min(-1), dexa+ vs. dexa-, NS) and during hyperinsulinemia (6.8 +/- 2.9 vs. 5.8 +/- 1.9 mL x g(-1) x min(-1), respectively, NS) tended to be (but were not) significantly higher after dexamethasone treatment. These results demonstrate that insulin acts as a vasodilatory hormone also in the coronary vasculature. Because the insulin-induced increment of myocardial flow reserve remained unchanged by dexamethasone pretreatment, centrally mediated sympathetic activation seems not to play a major role in regulating insulin action on myocardial perfusion in healthy subjects.
authors.affiliation: Turku PET Centre, Turku University, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Laine
authors.forename: P
authors.initials: P
authors.lastname: Nuutila
authors.forename: M
authors.initials: M
authors.lastname: Luotolahti
authors.forename: C
authors.initials: C
authors.lastname: Meyer
authors.forename: T
authors.initials: T
authors.lastname: Elomaa
authors.forename: P
authors.initials: P
authors.lastname: Koskinen
authors.forename: T
authors.initials: T
authors.lastname: Rönnemaa
authors.forename: J
authors.initials: J
authors.lastname: Knuuti
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D004452:Echocardiography / Q000187:drug effects; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption; D012039:Regional Blood Flow / Q000187:drug effects; D014055:Tomography, Emission-Computed; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D003907:Dexamethasone; D002784:Cholesterol; D000241:Adenosine; D009638:Norepinephrine; D004837:Epinephrine