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    The effect of endogenously released glucose, insulin, glucagon-like peptide 1, ghrelinon cardiac output, heart rate, stroke volume, and blood pressure

    Hlebowicz, Joanna; Lindstedt Ingemansson, Sandra; Bjrgell, Ola; Dencker, Magnus

    Published in:Cardiovascular Ultrasound


    Published: 2011-01-01

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    Citation for published version (APA):Hlebowicz, J., Lindstedt Ingemansson, S., Bjrgell, O., & Dencker, M. (2011). The effect of endogenouslyreleased glucose, insulin, glucagon-like peptide 1, ghrelin on cardiac output, heart rate, stroke volume, andblood pressure. Cardiovascular Ultrasound, 9(43). DOI: 10.1186/1476-7120-9-43

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  • RESEARCH Open Access

    The effect of endogenously released glucose,insulin, glucagon-like peptide 1, ghrelin oncardiac output, heart rate, stroke volume, andblood pressureJoanna Hlebowicz1*, Sandra Lindstedt2, Ola Bjrgell3 and Magnus Dencker4


    Background: Ingestion of a meal increases the blood flow to the gastrointestinal organs and affects the heart rate(HR), blood pressure and cardiac output (CO), although the mechanisms are not known. The aim of this study wasto evaluate the effect of endogenously released glucose, insulin, glucagon-like peptide 1 (GLP-1), ghrelin on CO,HR, stroke volume (SV), and blood pressure.

    Methods: Eleven healthy men and twelve healthy women ((mean SEM) aged: 26 0.2 y; body mass index: 21.8 0.1 kg/m2)) were included in this study. The CO, HR, SV, systolic and diastolic blood pressure, antral area, gastricemptying rate, and glucose, insulin, GLP-1 and ghrelin levels were measured.

    Results: The CO and SV at 30 min were significantly higher, and the diastolic blood pressure was significantlylower, than the fasting in both men and women (P < 0.05). In men, significant correlations were found betweenGLP-1 level at 30 min and SV at 30 min (P = 0.015, r = 0.946), and between ghrelin levels and HR (P = 0.013, r =0.951) at 110 min. Significant correlations were also found between the change in glucose level at 30 min and thechange in systolic blood pressure (P = 0.021, r = -0.681), and the change in SV (P = 0.008, r = -0.748) relative to thefasting in men. The insulin 0-30 min AUC was significantly correlated to the CO 0-30 min AUC (P = 0.002, r =0.814) in men. Significant correlations were also found between the 0-120 min ghrelin and HR AUCs (P = 0.007, r =0.966) in men. No statistically significant correlations were seen in women.

    Conclusions: Physiological changes in the levels of glucose, insulin, GLP-1 and ghrelin may influence the activity ofthe heart and the blood pressure. There may also be gender-related differences in the haemodynamic responsesto postprandial changes in hormone levels. The results of this study show that subjects should not eat immediatelyprior to, or during, the evaluation of cardiovascular interventions as postprandial affects may affect the results,leading to erroneous interpretation of the cardiovascular effects of the primary intervention.

    Trial registration number: NCT01027507

    BackgroundSeveral kinds of postprandial cardiovascular changeshave been reported in the literature. The postprandialblood flow in the superior mesenteric artery (SMA)seems to be approximately double the fasting value, andinitiates an increase in cardiac output (CO) [1].

    Postprandial CO increase has been suggested to resultfrom increases in the heart rate (HR) and stroke volume(SV). The postprandial blood flow in the SMA increasessimultaneously with the gradual increase in the CO,reaching a maximum 30 to 60 min after eating. A largemeal increases CO more, and for a longer time, than asmall meal [2]. However, the composition of the mealseems to be less important in this respect [3]. Theingestion of food has also been shown to decrease thediastolic blood pressure [4,5].

    * Correspondence: for Emergency, Department of Cardiology, Skne University Hospital,Malm, Lund University, SwedenFull list of author information is available at the end of the article

    Hlebowicz et al. Cardiovascular Ultrasound 2011, 9:43


    2011 Hlebowicz et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (, which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.

  • The autonomic innervation of the stomach and theheart is divided into the parasympathetic and sympa-thetic systems. The parasympathetic innervation is con-trolled by the vagus nerve, whose cell bodies are foundin the brainstem. The vagus nerve consists of 20% effer-ent fibres and 80% afferent sensory fibres, which trans-mit information to the brain [6]. The vagus nervemediates the adaptive relaxation of the proximal sto-mach, the fundic-antral co-ordination (by controlleddelivery of the food from the fundus to the antrum) andthe peristaltic contractions of the distal stomach after ameal [7]. Sympathetic stimulation increases the HR(positive chronotropy), inotropy and conduction velocity(positive dromotropy), whereas parasympathetic stimula-tion of the heart has the opposite effects [6]. Changes inHR, heart rate variability (HRV), and blood pressure aresome of the factors that may reflect the balance betweenthe sympathetic and parasympathetic nervous systems. Itappears that neural signals are less likely to be responsi-ble for the increase in CO [8]. In order to investigatedenervated hearts, Waaler at al. investigated subjectswith transplanted hearts and found that the CO, HRand SV increased in a similar way to that of controlsubjects [4,8]. It is still not known what causes thechanges in the pumping activity of the heart postpran-dially. Our hypothesis was that the intake of food wouldchange the activity of the heart due to postprandialchanges in the antral area, or levels of glucose, insulin,GLP-1 and ghrelin. It is known that insulin has positivechronotropic and inotropic effects on the heart [9], andthe hormone glucagon-like peptide 1 (GLP-1) has beenshown to improve left ventricular function [10,11]. Thehormone ghrelin has been shown to increase CO andstroke volume (SV) [12-15]. Postprandial haemodynamicchanges have been shown to resemble the effects ofvasodilator drugs [16,17]. The evaluation of cardiovascu-lar interventions postprandially may affect the results,leading to erroneous interpretation of the cardiovasculareffects of the primary intervention. The aim of thisstudy was to evaluate the effect of endogenouslyreleased glucose, insulin, GLP-1, ghrelin on CO, HR,stroke volume (SV), and blood pressure.

    MethodsTwenty-three healthy subjects (11 men, 12 women;(mean SEM) aged: 26 0.2 y (range: 18-33 y); bodymass index: 21.8 0.1 kg/m2 (range: 17.0-25.9 kg/m2))without symptoms or a history of gastrointestinal dis-ease, abdominal surgery or diabetes mellitus, wereincluded in this observational study. The mean waist:hipratio of the women was 0.74 0.02 and of the men 0.87 0.01. The subjects had no connective tissue disease orcerebrovascular or endocrine disease, and none was tak-ing any medication, except four women who were taking

    oral contraceptives. Three men were snuff users and onewas a smoker, while two of the women were snuff users.All subjects were recruited from the population ofsouthern Sweden.All subjects gave their written informed consent. The

    study was approved by the Ethics Committee of LundUniversity, and performed according to the HelsinkiDeclaration. The study started on 13 January 2009 andended on 18 September 2009. The trial is registered inthe US National Library of Medicine with the trial regis-tration number NCT01027507.The subjects were examined between 7.30 and 11.00 a.

    m. after an 8-h fast. Smoking and snuff-taking were pro-hibited 8 h prior to and during the examination. Thefasting blood glucose concentration of each subject wasmeasured on the day of the examination to ensure thatit was normal ( 7.0 mmol/L). If the subjects reportedgastrointestinal symptoms (diarrhoea or constipation)on the day of the study, the examination was postponed.The test meal consisted of 300 g rice pudding (AXA

    Goda Grten Risgrynsgrt; Lantmnnen AXA, Jrna,Sweden). The total caloric value of the meal was 330kcal: 10% from protein (9 g), 58% from carbohydrates(48 g) an


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