Effects of metoclopramide and metoclopramide/dopamine on blood pressure and insulin release in normotensive, hypertensive, and type 2 diabetic subjects.

The objective is to determine cardiovascular and insulin release effects under metoclopramide (MTC) and dopamine (DA) infusion by using an acute comparative design with the intravenous infusion of both drugs. We evaluated 15 normal (normotensive and normoglycemic) subjects, 13 hypertensive, and 15 type 2 diabetic subjects. Subjects were submitted to an experimental design in which we first gave them a 0.9% saline solution for 30 minutes, and then administered MTC at 7.5 microg kg min through an intravenous infusion during a period of 30 minutes. Although subjects were receiving MTC, we added an intravenous infusion of DA at 1-3 microg kg min during 30 minutes. Blood pressure, heart rate, serum lipid profile, and insulin levels were measured. Sympathetic reactivity by the cold pressor test was also measured. In normotensive subjects, there was a systolic blood pressure and heart rate increase during MTC plus DA infusion. In subjects with diabetes mellitus there was a heart rate increase without changes in blood pressure during the MTC plus DA infusion period. In hypertensive subjects, MTC induced a significant decrease of systolic and diastolic blood pressure. During MTC plus DA period there was an increase of heart rate but no significant changes in blood pressure. During cold pressor test in both diabetic and hypertensive subjects, there were significant increases of both blood pressure and heart rate. Insulin serum levels increased in normotensive and hypertensive subjects but were attenuated in subjects with diabetes mellitus. We conclude that there is a pharmacologic interaction between MTC and DA, that the pressor effects of DA are due to activation to beta and alpha adrenergic receptors, and that the cardiovascular effects of DA in type 2 diabetic subjects are attenuated by a probable defect in sympathetic system and to endothelial dysfunction.

Effect of drugs interacting with the dopaminergic receptors on glucose levels and insulin release in healthy and type 2 diabetic subjects.

Dopamine agonists play an important role in the regulation of the central nervous-cardiovascular, renal, and hormonal systems through stimulation of dopaminergic (DA1 and DA2) and alpha- and beta-adrenergic receptors. Several studies have shown that in fat and diabetic mice. The aim of the present study was to evaluate the interaction of the dopaminergic and endocrine systems by determining the effect of the dopaminergic antagonist, metoclopramide, and dopamine on insulin secretion and cardiovascular response by blockade and activation of dopamine receptors in healthy and type 2 diabetic subjects. Healthy subjects (n =15) and subjects with type 2 diabetes (n = 15) of both genders, aged 18 to 60 years, were recruited into this study. A comparative experimental design of 90 minutes was performed in which placebo (0.9% saline) was infused intravenously for the first 30 minutes followed by metoclopramide (7.5 microg/kg/min), a dopamine receptor antagonist for 30 minutes, and then metoclopramide (7.5 microg/kg/min) plus dopamine (0.5-3 microg/kg/min) for 30 minutes. The following clinical and biochemical parameters were measured at the beginning and then every 30 minutes of the experimental period (30', 60' and 90'): systolic-diastolic and mean arterial blood pressure, heart rate, serum glucose, insulin, triacylglycerides, and total cholesterol. Baseline glycosylated hemoglobin was measured and homeostasis model assessment for insulin resistance was calculated from insulin and glucose levels. Twelve-lead electrocardiograms were also obtained at these points. Dopamine infusion induced an increase in serum insulin, systolic blood pressure, and heart rate in healthy subjects but not in subjects with type 2 diabetes. Infusion of metoclopramide induced a hypotensive effect in healthy subjects, which was blunted by inclusion of dopamine in the infusion mixture. In subjects with diabetes, metoclopramide had no effect on blood pressure, but addition of dopamine raised systolic blood pressure. Neither metoclopramide nor dopamine altered significantly the lipid profile in healthy or diabetic subjects. Dopaminergic drugs increase serum insulin probably by interacting with dopaminergic receptors, but stimulation of beta-adrenergic receptors cannot be ruled out. Stimulation of cardiovascular dopamine receptors also caused modifications of hemodynamic parameters in healthy subjects, but apparently these receptors are attenuated in patients with type 2 diabetes probably as a result of endothelial dysfunction and alterations in the sympathetic nervous system sensitivity.

Relación entre dopamina e insulina en sujetos sanos y diabeticos tipo 2 / Relationship between dopamine and insulin in healthy subjects and type 2 diabetes

Los agonistas de la dopamina ejercen un papel importante en la regulación de los sistemas nervioso central, cardiovascular, renal y endocrino, por la estimulación de los receptores a y ß adrenérgicos y dopaminérgicos específicos DA1 y DA2. Diversos estudios demuestran que los agonistas dopaminérgicos mejoran la hiperglicemia y la hiperlipidemia en ratones obesos y diabéticos. Establecer la relación entre la activación de receptores dopaminérgicos y la secreción de insulina mediante el uso de Metoclopramida (MTC) y dopamina (DA) y determinar mediante variables hemodinámicas la respuesta a la activación de receptores dopaminergicos cardiovasculares en sujetos sanos y diabéticos tipo 2. Se seleccionaron 15 sujetos sanos (controles) y 15 diabéticos tipo 2, entre 29 y 53 años de edad, del sexo masculino y femenino. Se diseño un estudio experimental comparativo de 90 minutos es decir, se administraron infusiones intravenosas de dopamina a 0.5-3 µg/Kg y de MTC (DA2), a 7.5 µg/Kg/min. Se empleó como placebo solución fisiológica. Los parámetros estudiados, a 0', 30', 60' y 90 minutos, incluyeron: insulina, glicemia, hemoglobina glicosilada A1c, HOMA-IR, EKG de 12 derivaciones y medición de FC, PAS, PAD y PAM. Resultados: La dopamina (DA) produjo un incremento en la insulina plasmática, PAS y la frecuencia cardiaca en sujetos sanos, pero no en sujetos diabéticos tipo 2. La MTC indujo un efecto hipotensor en sujetos sanos. MTC y DA, no producen modificaciones significativas en el perfil lipidico de sujetos sanos y diabéticos. Las drogas dopaminèrgicas (MTC y DA) median vía activación de receptores dopaminèrgicos pancreáticos un incremento en la insulina plasmática, y al actuar sobre receptores dopaminèrgicos cardiovasculares modifican las variables hemodinámicas, modificación que es atenuada en pacientes diabéticos probablemente por disfunción endotelial y disautonomìa simpática.