This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laine, H. Articles by Knuuti, J. Search for Related Content PubMed PubMed Citation Articles by Laine, H. Articles by Knuuti, J.

Insulin-Induced Increment of Coronary Flow Reserve Is Not Abolished by Dexamethasone in Healthy Young Men¹

Turku PET Centre (H.L., P.N., T.E., J.K.) and Departments of Medicine (P.N., T.R.), Clinical Physiology (M.L.), and Clinical Chemistry (P.K.) of Turku University, FIN-20521 Turku, Finland; and Department of Clinical Physiology and Nuclear Medicine (C.M.), Rigshospitalet University Hospital, DK-2100 Copenhagen, Denmark

Address correspondence and requests for reprints to: Dr. Hanna Laine, Turku PET Centre, Turku University Central Hospital, P.O. Box 52, FIN-20521 Turku, Finland. E-mail: hannal{at}pet.tyks.fi

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·g ^-1·min ^-1; blood pressure, 118 ± 10/65 ± 8 mm Hg) at fasting and during euglycemic hyperinsulinemic clamp (1 mU·kg^-1·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·g^-1·min^-1, and a significant increase in flow was detected after adenosine infusion (140 µg/kg·min for 5 min iv), 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·g^-1·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·g^-1·min^-1, dexa+ vs. dexa-, not significant (NS)], the adenosine stimulated flow (3.56 ± 1.49 vs. 3.38 ± 0.97 mL·g^-1·min^-1, respectively, NS), or the hyperinsulinemic adenosine-stimulated blood flow (4.68 ± 1.74 vs. 4.28 ± 1.57 mL·g^-1·min^-1, respectively, NS). Coronary flow reserves in the basal state (5.3 ± 2.7 vs. 4.6 ± 1.2 mL·g^-1·min^-1, dexa+ vs. dexa-, NS) and during hyperinsulinemia (6.8 ± 2.9 vs. 5.8 ± 1.9 mL·g^-1·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.

This article has been cited by other articles:

				Z. Liu Insulin at physiological concentrations increases microvascular perfusion in human myocardium Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1250 - E1255. [Abstract] [Full Text] [PDF]

				R. Muniyappa, M. Montagnani, K. K. Koh, and M. J. Quon Cardiovascular Actions of Insulin Endocr. Rev., August 1, 2007; 28(5): 463 - 491. [Abstract] [Full Text] [PDF]

				K. M. Canniff, M. S. Smith, D. B. Lacy, P. E. Williams, and M. C. Moore Glucagon secretion and autonomic signaling during hypoglycemia in late pregnancy Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2006; 291(3): R788 - R795. [Abstract] [Full Text] [PDF]

				M. Srinivasan, P. Herrero, J. B. McGill, J. Bennik, B. Heere, D. Lesniak, V. G. Davila-Roman, and R. J. Gropler The Effects of Plasma Insulin and Glucose on Myocardial Blood Flow in Patients With Type 1 Diabetes Mellitus J. Am. Coll. Cardiol., July 5, 2005; 46(1): 42 - 48. [Abstract] [Full Text] [PDF]

				E. Grossini, A. Battaglia, G. Bona, D. A. S. G. Mary, C. Molinari, and G. Vacca The effects of insulin on mesenteric blood flow in anaesthetized pigs Exp Physiol, July 1, 2004; 89(4): 363 - 371. [Abstract] [Full Text] [PDF]

				H Laine, J Sundell, P Nuutila, O T Raitakari, M Luotolahti, T Ronnemaa, T Elomaa, P Koskinen, and J Knuuti Insulin induced increase in coronary flow reserve is abolished by dexamethasone in young men with uncomplicated type 1 diabetes Heart, March 1, 2004; 90(3): 270 - 276. [Abstract] [Full Text] [PDF]

				J. Sundell and J. Knuuti Insulin and myocardial blood flow Cardiovasc Res, February 1, 2003; 57(2): 312 - 319. [Abstract] [Full Text] [PDF]

				E. Yetkin, K. Senen, M. Ileri, R. Atak, B. Battaoglu, O. Yetkin, I. Tandogan, H. Turhan, and S. Cehreli Identification of Viable Myocardium in Patients with Chronic Coronary Artery Disease and Myocardial Dysfunction: Comparison of Low-Dose Dobutamine Stress Echocardiography and Echocardiography During Glucose-Insulin-Potassium Infusion Angiology, November 1, 2002; 53(6): 671 - 676. [Abstract] [PDF]

				J. Sundell, P. Nuutila, H. Laine, M. Luotolahti, K. Kalliokoski, O. Raitakari, and J. Knuuti Dose-Dependent Vasodilating Effects of Insulin on Adenosine-Stimulated Myocardial Blood Flow Diabetes, April 1, 2002; 51(4): 1125 - 1130. [Abstract] [Full Text] [PDF]

				P. Iozzo, P. Chareonthaitawee, M. Di Terlizzi, D. J. Betteridge, E. Ferrannini, and P. G. Camici Regional myocardial blood flow and glucose utilization during fasting and physiological hyperinsulinemia in humans Am J Physiol Endocrinol Metab, May 1, 2002; 282(5): E1163 - E1171. [Abstract] [Full Text] [PDF]